Skip to main content

Advertisement

SpringerLink
Log in

Long non-coding RNAs in metabolic disorders: pathogenetic relevance and potential biomarkers and therapeutic targets

  • Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

It has been suggested that dysregulation of long non-coding RNAs (lncRNAs) could be associated with the incidence and development of metabolic disorders.

Aim

Accordingly, this narrative review described the molecular mechanisms of lncRNAs in the development of metabolic diseases including insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), cirrhosis, and coronary artery diseases (CAD). Furthermore, we investigated the up-to-date findings on the association of deregulated lncRNAs in the metabolic disorders, and potential use of lncRNAs as biomarkers and therapeutic targets.

Conclusion

LncRNAs/miRNA/regulatory proteins axis plays a crucial role in progression of metabolic disorders and may be used in development of therapeutic and diagnostic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

lncRNA:

Long non-coding RNA

ncRNA:

Noncoding RNA

NAFLD:

Nonalcoholic fatty liver disease

NGS:

Next-generation sequencing

rRNA:

Ribosomal RNA

tRNA:

Transfer RNA

ScRNA:

Small cytoplasmic/ conditional RNA

miRNA:

MicroRNA

SnoRNA:

Small nucleolar RNA

LincRNA:

Long intergenic noncoding RNA

ORF:

Open reading frame

T2D:

Type 2 diabetes

AMPK:

AMP-activated protein kinase

DUSP27:

Dual specificity phosphatase 27

INSR:

Insulin receptor

IRS-2:

Insulin receptor substrate 2

IDE:

Insulin-degrading enzyme

HnRNPA1:

Heterogeneous nuclear ribonucleoprotein A1

CPT1b:

Carnitine palmitoyltransferase 1

PGC1a:

Proliferator-activated receptor gamma coactivator 1-alpha

SREBP-1c:

Sterol regulatory element-binding transcription factor 1

MALAT1:

Metastasis associated lung adenocarcinoma transcript 1

GCK:

Glucokinase

hnRNPL:

Heterogenous nuclear ribonucleoprotein L

SHGL:

Suppressor of hepatic gluconeogenesis and lipogenesis

CALM:

Clathrin assembly lymphoid myeloid leukemia

FoxO1:

Forkhead box protein O1

ATF4:

Activating transcription factor 4

G6pase:

Glucose-6- phosphatase

PEPCK:

Phosphoenolpyruvate carboxykinase

MEG3:

Maternally expressed 3 gene

HOTAIR:

HOX transcript antisense RNA

GSK:

Glycogen synthase kinase

USP-10:

Ubiquitin specific peptidase 10

Mirt2:

Myocardial infraction associated transcript 2

SRA:

Steroid receptor RNA activator

PPARγ:

Peroxisome proliferator-activated receptor gamma

TNF-α:

Tumor necrosis factor alpha

MCP-1:

Monocyte chemoattractant protein-1

SIRT1:

Sirtuin 1

GLUT4:

Glucose transporter type 4

TUG1:

Taurine upregulated gene 1

PTEN:

Phosphatase and tensin homolog

PIP3:

Phosphatidylinositol (3,4,5)-trisphosphate

HOMA-IR:

Homeostatic model assessment for insulin resistance

Pdx-1:

Pancreatic and duodenal homeobox 1

GAS5:

Growth arrest-specific 5

GLUT2:

Glucose transporter 2

Tcf7l2:

Transcription factor 7-like 2

Bhmt-AS:

Betaine-homocysteine methyltransferase-antisense

DN:

Diabetic nephropathy

CASC2:

Cancer susceptibility candidate 2

ZEB1-AS1:

Zinc finger E‑box‑binding homeobox 1‑antisense 1

DKD:

Diabetic kidney diseases

IL-6:

Interleukin 6

EZH2:

Enhancer of zeste homolog 2

Dlx6os1:

Distal-less homeobox 6, opposite strand 1

MMP9:

Matrix metallopeptidase 9

Rpph1:

Ribonuclease P RNA component H1

MEK:

Mitogen-activated protein kinase kinase

ERK:

Extracellular signal-regulated kinase

PVT1:

Plasmacytoma variant translocation 1

MIAT:

Myocardial infarction associated transcript

Nrf2:

Nuclear factor erythroid-2 related factor 2

ErbB1:

Epidermal growth factor receptor-1

Erbb4-IR:

Erb-b2 receptor tyrosine kinase 4- immunoreactivity

CDKN2B-AS1:

CDKN2B antisense RNA 1

HMGA2:

High mobility group AT-hook 2

DR:

Diabetic retinopathy

RNCR3:

Retinal non-coding RNA3

KLF2:

Kruppel like factor 2

HOTTIP:

HOXA distal transcript antisense RNA

MAPK:

Mitogen activated kinase-like protein

Sox2OT:

SOX2 overlapping transcript

HO-1:

Heme oxygenase 1

TGF-β1:

Transforming growth factor beta 1

VEGF:

Vascular endothelial growth factor

PI3K:

Phosphatidylinositol 3-kinase

BANCR:

BRAF-activated non-protein coding RNA

XBP1:

X-box binding protein 1

PINT:

P53 induced transcript

SNHG7:

Small nucleolar RNA host gene 7

DNP:

Diabetic neuropathic pain

siRNA:

Small interfering RNA

EMNVs:

Extracellular vesicle-mimetic nanovesicles

HIF-1α:

Hypoxia-inducible factor 1-alpha

DCM:

Diabetic cardiomyopathy

VDAC1:

Voltage-dependent anion-selective channel 1

mTOR:

Mechanistic target of rapamycin kinase

Kcnq1ot1:

KCNQ1 opposite strand/antisense transcript 1

DAPK2:

Death associated protein kinase 2

PDCD4:

Programmed cell death 4

ANRIL:

Antisense non-coding RNA in the INK4 locus

NLRP3:

NLR family pyrin domain containing 3

IGF:

Insulin growth factor

MyD88:

Myeloid differentiation primary response gene 88

IRAK1:

Interleukin 1 receptor associated kinase 1

TRAF6:

TNF receptor associated factor 6

LEGLTBC:

Low expression in glucolipotoxicity-treated beta cells

GDM:

Gestational diabetes mellitus

Cyp2e1:

Cytochrome P450 family 2 subfamily E member 1

Atp5b:

ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit

Hibch:

3-Hydroxyisobutyryl-CoA hydrolase

Cnbp:

CCHC-type zinc finger nucleic acid binding protein

Frmd6:

FERM domain containing 6

Ptchd3:

Patched domain containing 3

Paral1:

PPARG activating RBM14 associated lncRNA 1

WAT:

White adipose tissue

NEAT1:

Nuclear enriched abundant transcript 1

ADSCs:

Adipose tissue-derived mesenchymal stem cells

HCP5:

HLA complex P5

MIR31HG:

MIR31 host gene

BAT:

Brown adipose tissue

UCP-1:

Uncoupling protein 1

hADSCs:

Human adipose-derived stem cells

CEBPα:

CCAAT enhancer binding protein alpha

DGAT2:

Diacylglycerol O-acyltransferase 2

CIDEC:

Cell death-inducing DFFA-like effector c

DGAT2:

Diacylglycerol O-acyltransferase 2

FLRL:

Fatty liver-related lncRNA

HFD:

High fat diet

HULC:

Hepatocellular carcinoma up-regulated long non-coding RNA

RIPK1:

Receptor interacting serine/threonine kinase 1

USP-4:

Ubiquitin specific peptidase 4

DNMT1:

DNA methyltransferase 1

Timp1:

TIMP metallopeptidase inhibitor 1

Rac1:

Rac family small GTPase 1

CXCL5:

C-X-C motif chemokine ligand 5

STAT3:

Signal transducer and activator of transcription 3

TLR4:

Toll-like receptor 4

PCNA:

Proliferating cell nuclear antigen

CLIP1:

CAP-Gly domain containing linker protein 1

LYVE1:

Lymphatic vessel endothelial hyaluronan receptor 1

ITSN1:

Intersectin 1

ceRNA:

Competitive endogenous RNA

References

  1. Lowe R, Shirley N, Bleackley M, Dolan S, Shafee T (2017) Transcriptomics technologies. PLoS Comput Biol 13(5):e1005457. https://doi.org/10.1371/journal.pcbi.1005457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Qian X, Ba Y, Zhuang Q, Zhong G (2014) RNA-Seq technology and its application in fish transcriptomics. OMICS 18(2):98–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McGettigan PA (2013) Transcriptomics in the RNA-seq era. Curr Opin Chem Biol 17(1):4–11. https://doi.org/10.1016/j.cbpa.2012.12.008

    Article  CAS  PubMed  Google Scholar 

  4. Hemberg M, Gray JM, Cloonan N, Kuersten S, Grimmond S, Greenberg ME, Kreiman G (2012) Integrated genome analysis suggests that most conserved non-coding sequences are regulatory factor binding sites. Nucleic Acids Res 40(16):7858–7869. https://doi.org/10.1093/nar/gks477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kopp F, Mendell JT (2018) Functional classification and experimental dissection of long noncoding RNAs. Cell 172(3):393–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hacisuleyman E, Goff LA, Trapnell C, Williams A, Henao-Mejia J, Sun L, McClanahan P, Hendrickson DG, Sauvageau M, Kelley DR (2014) Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nat Struct Mol Biol 21(2):198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39(6):925–938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. López-Urrutia E, Bustamante Montes LP, de Guevara Cervantes DL, Pérez-Plasencia C, Campos-Parra AD (2019) Crosstalk between long non-coding RNAs, Micro-RNAs and mRNAs: deciphering molecular mechanisms of master regulators in cancer. Front Oncol. https://doi.org/10.3389/fonc.2019.00669

    Article  PubMed  PubMed Central  Google Scholar 

  9. Giroud M, Scheideler M (2017) Long non-coding RNAs in metabolic organs and energy homeostasis. Int J Mol Sci. https://doi.org/10.3390/ijms18122578

    Article  PubMed  PubMed Central  Google Scholar 

  10. Galgani J, Ravussin E (2008) Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond) 32(Suppl 7):S109-119. https://doi.org/10.1038/ijo.2008.246

    Article  CAS  Google Scholar 

  11. Martínez JA, Milagro FI, Claycombe KJ, Schalinske KL (2014) Epigenetics in adipose tissue, obesity, weight loss, and diabetes. Adv Nutr 5(1):71–81. https://doi.org/10.3945/an.113.004705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ji E, Kim C, Kim W (1863) Lee EK (2020) Role of long non-coding RNAs in metabolic control. Biochim Biophys Acta Gene Regul Mech 4:194348. https://doi.org/10.1016/j.bbagrm.2018.12.006

    Article  CAS  Google Scholar 

  13. Sathishkumar C, Prabu P, Mohan V, Balasubramanyam M (2018) Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes. Hum Genomics 12(1):41. https://doi.org/10.1186/s40246-018-0173-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zaman G (2020) Pathogenesis of insulin resistance. Cellular metabolism and related disorders, IntechOpen

    Google Scholar 

  15. Motterle A, Gattesco S, Peyot ML, Esguerra JLS, Gomez-Ruiz A, Laybutt DR, Gilon P, Burdet F, Ibberson M, Eliasson L, Prentki M, Regazzi R (2017) Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes. Mol Metab 6(11):1407–1418. https://doi.org/10.1016/j.molmet.2017.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Morán I, Akerman I, Van De Bunt M, Xie R, Benazra M, Nammo T, Arnes L, Nakić N, García-Hurtado J, Rodríguez-Seguí S (2012) Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab 16(4):435–448

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Zhang BB, Zhou G, Li C (2009) AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 9(5):407–416

    Article  PubMed  CAS  Google Scholar 

  18. Hardie DG (2015) AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr Opin Cell Biol 33:1–7

    Article  CAS  PubMed  Google Scholar 

  19. Salminen A, Kaarniranta K, Kauppinen A (2016) Age-related changes in AMPK activation: role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways. Ageing Res Rev 28:15–26

    Article  CAS  PubMed  Google Scholar 

  20. Geng T, Liu Y, Xu Y, Jiang Y, Zhang N, Wang Z, Carmichael GG, Taylor HS, Li D, Huang Y (2018) H19 lncRNA promotes skeletal muscle insulin sensitivity in part by targeting AMPK. Diabetes 67(11):2183–2198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tian Y, Xu J, Du X, Fu X (2018) The interplay between noncoding RNAs and insulin in diabetes. Cancer Lett 419:53–63

    Article  CAS  PubMed  Google Scholar 

  22. Roden M (2005) Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes. Int J Obes 29(2):S111–S115

    Article  CAS  Google Scholar 

  23. Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384–387

    Article  CAS  PubMed  Google Scholar 

  24. Gui W, Zhu WF, Zhu Y, Tang S, Zheng F, Yin X, Lin X, Li H (2020) LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1. Cell Commun Signaling 18(1):1–14

    Article  CAS  Google Scholar 

  25. Kotzka J, Knebel B, Janssen OE, Schaefer J, Soufi M, Jacob S, Nitzgen U, Muller-Wieland D (2011) Identification of a gene variant in the master regulator of lipid metabolism SREBP-1 in a family with a novel form of severe combined hypolipidemia. Atherosclerosis 218(1):134–143

    Article  CAS  PubMed  Google Scholar 

  26. Yan C, Chen J, Chen N (2016) Long noncoding RNA MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability. Sci Rep 6(1):1–11

    CAS  Google Scholar 

  27. Ruan X, Li P, Cangelosi A, Yang L, Cao H (2016) A long non-coding RNA, lncLGR, regulates hepatic glucokinase expression and glycogen storage during fasting. Cell Rep 14(8):1867–1875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang J, Yang W, Chen Z, Chen J, Meng Y, Feng B, Sun L, Dou L, Li J, Cui Q (2018) Long noncoding RNA lncSHGL recruits hnRNPA1 to suppress hepatic gluconeogenesis and lipogenesis. Diabetes 67(4):581–593

    Article  CAS  PubMed  Google Scholar 

  29. Li K, Zhang J, Yu J, Liu B, Guo Y, Deng J, Chen S, Wang C, Guo F (2015) MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4. J Biol Chem 290(13):8185–8195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhu X, Li H, Wu Y, Zhou J, Yang G, Wang W (2019) lncRNA MEG3 promotes hepatic insulin resistance by serving as a competing endogenous RNA of miR-214 to regulate ATF4 expression. Int J Mol Med 43(1):345–357

    CAS  PubMed  Google Scholar 

  31. Li M, Guo Y, Wang XJ, Duan BH, Li L (2018) HOTAIR participates in hepatic insulin resistance via regulating SIRT1. Eur Rev Med Pharmacol Sci 22(22):7883–7890. https://doi.org/10.26355/eurrev_201811_16414

    Article  CAS  PubMed  Google Scholar 

  32. Luo P, Qin C, Zhu L, Fang C, Zhang Y, Zhang H, Pei F, Tian S, Zhu XY, Gong J, Mao Q, Xiao C, Su Y, Zheng H, Xu T, Lu J, Zhang J (2018) Ubiquitin-specific peptidase 10 (USP10) inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6. Hepatology 68(5):1786–1803. https://doi.org/10.1002/hep.30062

    Article  CAS  PubMed  Google Scholar 

  33. Zhang B, Li H, Li D, Sun H, Li M, Hu H (2019) Long noncoding RNA Mirt2 upregulates USP10 expression to suppress hepatic steatosis by sponging miR-34a-5p. Gene 700:139–148

    Article  CAS  PubMed  Google Scholar 

  34. Liu S, Sheng L, Miao H, Saunders TL, MacDougald OA, Koenig RJ, Xu B (2014) SRA gene knockout protects against diet-induced obesity and improves glucose tolerance. J Biol Chem 289(19):13000–13009. https://doi.org/10.1074/jbc.M114.564658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang Y, Gu M, Ma Y, Peng Y (2020) LncRNA TUG1 reduces inflammation and enhances insulin sensitivity in white adipose tissue by regulating miR-204/SIRT1 axis in obesity mice. Mol Cell Biochem 475(1–2):171–183. https://doi.org/10.1007/s11010-020-03869-6

    Article  CAS  PubMed  Google Scholar 

  36. Butler M, McKay RA, Popoff IJ, Gaarde WA, Witchell D, Murray SF, Dean NM, Bhanot S, Monia BP (2002) Specific inhibition of PTEN expression reverses hyperglycemia in diabetic mice. Diabetes 51(4):1028–1034

    Article  CAS  PubMed  Google Scholar 

  37. Yang L, Wang X, Guo H, Zhang W, Wang W, Ma H (2019) Whole transcriptome analysis of obese adipose tissue suggests u001kfc.1 as a potential regulator to glucose homeostasis. Front Genet 10:1133. https://doi.org/10.3389/fgene.2019.01133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ebrahimi R, Toolabi K, Jannat Ali Pour N, Mohassel Azadi S, Bahiraee A, Zamani-Garmsiri F, Emamgholipour S (2020) Adipose tissue gene expression of long non-coding RNAs; MALAT1, TUG1 in obesity: is it associated with metabolic profile and lipid homeostasis-related genes expression? Diabetol Metab Syndr 12:36. https://doi.org/10.1186/s13098-020-00544-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Andrali SS, Sampley ML, Vanderford NL, Özcan S (2008) Glucose regulation of insulin gene expression in pancreatic β-cells. Biochem J 415(1):1–10

    Article  CAS  PubMed  Google Scholar 

  40. You L, Wang N, Yin D, Wang L, Jin F, Zhu Y, Yuan Q, De W (2016) Downregulation of long noncoding RNA Meg3 affects insulin synthesis and secretion in mouse pancreatic beta cells. J Cell Physiol 231(4):852–862. https://doi.org/10.1002/jcp.25175

    Article  CAS  PubMed  Google Scholar 

  41. Jin F, Wang N, Zhu Y, You L, Wang L, De W, Tang W (2017) Downregulation of long noncoding RNA gas5 affects cell cycle and insulin secretion in mouse pancreatic β cells. Cell Physiol Biochem 43(5):2062–2073. https://doi.org/10.1159/000484191

    Article  CAS  PubMed  Google Scholar 

  42. Ruan Y, Lin N, Ma Q, Chen R, Zhang Z, Wen W, Chen H, Sun J (2018) Circulating LncRNAs analysis in patients with type 2 diabetes reveals novel genes influencing glucose metabolism and islet β-cell function. Cell Physiol Biochem 46(1):335–350

    Article  CAS  PubMed  Google Scholar 

  43. Yin D-d, Zhang E-b, You L-h, Wang N, Wang L-t, Jin F-y, Zhu Y-n, Cao L-h, Yuan Q-x, De W (2015) Downregulation of lncRNA TUG1 affects apoptosis and insulin secretion in mouse pancreatic β cells. Cell Physiol Biochem 35(5):1892–1904

    Article  CAS  PubMed  Google Scholar 

  44. Basu R, Schwenk WF, Rizza RA (2004) Both fasting glucose production and disappearance are abnormal in people with “mild” and “severe” type 2 diabetes. Am J Physiol-Endocrinol Metab 287(1):E55–E62

    Article  CAS  PubMed  Google Scholar 

  45. Zhang F, Xu X, Zhang Y, Zhou B, He Z, Zhai Q (2013) Gene expression profile analysis of type 2 diabetic mouse liver. PLoS ONE 8(3):e57766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Goyal N, Sivadas A, Shamsudheen K, Jayarajan R, Verma A, Sivasubbu S, Scaria V, Datta M (2017) RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output. Sci Rep 7(1):1–12

    Article  CAS  Google Scholar 

  47. Shen X, Zhang Y, Zhang X, Yao Y, Zheng Y, Cui X, Liu C, Wang Q, Li JZ (2019) Long non-coding RNA Bhmt-AS attenuates hepatic gluconeogenesis via modulation of Bhmt expression. Biochem Biophys Res Commun 516(1):215–221

    Article  CAS  PubMed  Google Scholar 

  48. Song M, Zou L, Peng L, Liu S, Wu B, Yi Z, Gao Y, Zhang C, Xu H, Xu Y (2017) LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats. Endocr Res 42(3):180–190

    CAS  PubMed  Google Scholar 

  49. Mellitus D (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28(S37):S5–S10

    Google Scholar 

  50. Deshpande AD, Harris-Hayes M, Schootman M (2008) Epidemiology of diabetes and diabetes-related complications. Phys Ther 88(11):1254–1264

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kato M, Wang M, Chen Z, Bhatt K, Oh HJ, Lanting L, Deshpande S, Jia Y, Lai JY, O’Connor CL (2016) An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy. Nat Commun 7(1):1–16

    Article  Google Scholar 

  52. Tang W, Zhang D, Ma X (2017) RNA-sequencing reveals genome-wide long non-coding RNAs profiling associated with early development of diabetic nephropathy. Oncotarget 8(62):105832

    Article  PubMed  PubMed Central  Google Scholar 

  53. Wen L, Zhang Z, Peng R, Zhang L, Liu H, Peng H, Sun Y (2019) Whole transcriptome analysis of diabetic nephropathy in the db/db mouse model of type 2 diabetes. J Cell Biochem 120(10):17520–17533

    Article  CAS  PubMed  Google Scholar 

  54. Guo G, Ren S, Kang Y, Liu Y, Duscher D, Machens HG, Chen Z (2019) Microarray analyses of lncRNAs and mRNAs expression profiling associated with diabetic peripheral neuropathy in rats. J Cell Biochem 120(9):15347–15359

    Article  CAS  PubMed  Google Scholar 

  55. Yang Y, Lv X, Fan Q, Wang X, Xu L, Lu X, Chen T (2019) Analysis of circulating lncRNA expression profiles in patients with diabetes mellitus and diabetic nephropathy: differential expression profile of circulating lncRNA. Clin Nephrol 92(1):25–35. https://doi.org/10.5414/cn109525

    Article  CAS  PubMed  Google Scholar 

  56. Gao J, Wang W, Wang F, Guo C (2018) LncRNA-NR_033515 promotes proliferation, fibrogenesis and epithelial-to-mesenchymal transition by targeting miR-743b-5p in diabetic nephropathy. Biomed Pharmacother 106:543–552

    Article  CAS  PubMed  Google Scholar 

  57. Wang L, Su N, Zhang Y, Wang G (2018) Clinical significance of serum lncRNA cancer susceptibility candidate 2 (CASC2) for chronic renal failure in patients with type 2 diabetes. Med Sci Monit 24:6079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Li Y, Zheng L-l, Huang D-g, Cao H, Gao Y-h, Fan Z-c (2020) LNCRNA CDKN2B-AS1 regulates mesangial cell proliferation and extracellular matrix accumulation via miR-424-5p/HMGA2 axis. Biomed Pharmacother 121:109622

    Article  CAS  PubMed  Google Scholar 

  59. Ge X, Xu B, Xu W, Xia L, Xu Z, Shen L, Peng W, Huang S (2019) Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR-221 and modulating SIRT1 expression. Aging (Albany NY) 11(20):8745

    Article  CAS  Google Scholar 

  60. Song Y, Miao C, Wang J (2019) LncRNA ZEB1-AS1 inhibits renal fibrosis in diabetic nephropathy by regulating the miR-217/MAFB axis. RSC Adv 9(52):30389–30397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Majumder S, Hadden MJ, Thieme K, Batchu SN, Niveditha D, Chowdhury S, Yerra VG, Advani SL, Bowskill BB, Liu Y (2019) Dysregulated expression but redundant function of the long non-coding RNA HOTAIR in diabetic kidney disease. Diabetologia 62(11):2129–2142

    Article  CAS  PubMed  Google Scholar 

  62. Liu B, Qiang L, Wang G, Duan Q, Liu J (2019) LncRNA MALAT1 facilities high glucose induced endothelial to mesenchymal transition and fibrosis via targeting miR-145/ZEB2 axis. Eur Rev Med Pharmacol Sci 23(8):3478–3486

    CAS  PubMed  Google Scholar 

  63. Wu D, Cheng Y-g, Huang X, Zhong M-w, Liu S-z, Hu S-y (2018) Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model. J Physiol Biochem 74(3):431–439

    Article  PubMed  Google Scholar 

  64. Wang M, Wang S, Yao D, Yan Q, Lu W (2016) A novel long non-coding RNA CYP4B1-PS1-001 regulates proliferation and fibrosis in diabetic nephropathy. Mol Cell Endocrinol 426:136–145

    Article  CAS  PubMed  Google Scholar 

  65. Wang J, Pan J, Li H, Long J, Fang F, Chen J, Zhu X, Xiang X, Zhang D (2018) lncRNA ZEB1-AS1 was suppressed by p53 for renal fibrosis in diabetic nephropathy. Molecular Ther-Nucleic Acids 12:741–750

    Article  CAS  Google Scholar 

  66. Li Z, Yu Z, Meng X, Yu P (2018) LncRNA LINC00968 accelerates the proliferation and fibrosis of diabetic nephropathy by epigenetically repressing p21 via recruiting EZH2. Biochem Biophys Res Commun 504(2):499–504

    Article  CAS  PubMed  Google Scholar 

  67. Cheng J, Cheng L, Tang Y, Li H, Peng W, Huang S (2018) Inhibition of lncRNA Dlx6os1 decreases cell proliferation and fibrosis and increases cell apoptosis in diabetic nephropathy. Int J Clin Exp Pathol 11(7):3302

    PubMed  PubMed Central  Google Scholar 

  68. Zhang L, Zhao S, Zhu Y (2020) Long noncoding RNA growth arrest-specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2. FASEB J 34(2):2703–2714

    Article  CAS  PubMed  Google Scholar 

  69. Zhang P, Sun Y, Peng R, Chen W, Fu X, Zhang L, Peng H, Zhang Z (2019) Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3. Cell Death Dis 10(7):1–16

    Article  Google Scholar 

  70. Liu D-W, Zhang J-H, Liu F-X, Wang X-T, Pan S-K, Jiang D-K, Zhao Z-H, Liu Z-S (2019) Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. Exp Mol Med 51(8):1–15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Che X, Deng X, Xie K, Wang Q, Yan J, Shao X, Ni Z, Ying L (2019) Long noncoding RNA MEG3 suppresses podocyte injury in diabetic nephropathy by inactivating Wnt/β-catenin signaling. PeerJ 7:e8016

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Zhou L, Xu D-y, Sha W-g, Shen L, Lu G-y, Yin X (2015) Long non-coding MIAT mediates high glucose-induced renal tubular epithelial injury. Biochem Biophys Res Commun 468(4):726–732

    Article  CAS  PubMed  Google Scholar 

  73. Sun SF, Tang PMK, Feng M, Xiao J, Huang XR, Li P, Ma RCW, Lan HY (2018) Novel lncRNA Erbb4-IR promotes diabetic kidney injury in db/db mice by targeting miR-29b. Diabetes 67(4):731–744. https://doi.org/10.2337/db17-0816

    Article  CAS  PubMed  Google Scholar 

  74. Awata T, Yamashita H, Kurihara S, Morita-Ohkubo T, Miyashita Y, Katayama S, Mori K, Yoneya S, Kohda M, Okazaki Y (2014) A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA. PLoS ONE 9(11):e111715

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Shan K, Li C-P, Liu C, Liu X, Yan B (2017) RNCR3: a regulator of diabetes mellitus-related retinal microvascular dysfunction. Biochem Biophys Res Commun 482(4):777–783

    Article  CAS  PubMed  Google Scholar 

  76. Liu C, Li C-p, Wang J-J, Shan K, Liu X, Yan B (2016) RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis. Biochem Biophys Res Commun 479(2):198–203

    Article  CAS  PubMed  Google Scholar 

  77. Sun Y, Liu Y (2018) LncRNA HOTTIP improves diabetic retinopathy by regulating the p38-MAPK pathway. Eur Rev Med Pharmacol Sci 22(10):2941

    CAS  PubMed  Google Scholar 

  78. Li C-P, Wang S-H, Wang W-Q, Song S-G, Liu X-M (2017) Long noncoding RNA-Sox2OT knockdown alleviates diabetes mellitus-induced retinal ganglion cell (RGC) injury. Cell Mol Neurobiol 37(2):361–369

    Article  CAS  PubMed  Google Scholar 

  79. Zhang D, Qin H, Leng Y, Li X, Zhang L, Bai D, Meng Y, Wang J (2018) LncRNA MEG3 overexpression inhibits the development of diabetic retinopathy by regulating TGF-β1 and VEGF. Exp Ther Med 16(3):2337–2342

    PubMed  PubMed Central  Google Scholar 

  80. Qiu G-Z, Tian W, Fu H-T, Li C-P, Liu B (2016) Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. Biochem Biophys Res Commun 471(1):135–141

    Article  CAS  PubMed  Google Scholar 

  81. Gong W, Zhu G, Li J, Yang X (2018) LncRNA MALAT1 promotes the apoptosis and oxidative stress of human lens epithelial cells via p38MAPK pathway in diabetic cataract. Diabetes Res Clin Pract 144:314–321

    Article  CAS  PubMed  Google Scholar 

  82. Zhang Y-L, Hu H-Y, You Z-P, Li B-Y, Shi K (2020) Targeting long non-coding RNA MALAT1 alleviates retinal neurodegeneration in diabetic mice. Int J Ophthalmol 13(2):213

    Article  PubMed  PubMed Central  Google Scholar 

  83. Yu L, Fu J, Yu N, Wu Y, Han N (2020) Long noncoding RNA MALAT1 participates in the pathological angiogenesis of diabetic retinopathy in an oxygen-induced retinopathy mouse model by sponging miR-203a-3p. Can J Physiol Pharmacol 98(4):219–227

    Article  CAS  PubMed  Google Scholar 

  84. Liu P, Jia S-B, Shi J-M, Li W-J, Tang L-S, Zhu X-H, Tong P (2019) LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b/VE-cadherin axis. Biosci Rep. https://doi.org/10.1042/BSR20181469

  85. Zhang X, Zou X, Li Y, Wang Y (2019) Downregulation of lncRNA BANCR participates in the development of retinopathy among diabetic patients. Exp Ther Med 17(5):4132–4138

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Li Q, Pang L, Yang W, Liu X, Su G, Dong Y (2018) Long non-coding RNA of myocardial infarction associated transcript (LncRNA-MIAT) promotes diabetic retinopathy by upregulating transforming growth factor-β1 (TGF-β1) signaling. Med Sci Monit 24:9497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Yan B, Yao J, Liu J-Y, Li X-M, Wang X-Q, Li Y-J, Tao Z-F, Song Y-C, Chen Q, Jiang Q (2015) lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 116(7):1143–1156

    Article  CAS  PubMed  Google Scholar 

  88. Luo R, Xiao F, Wang P, Hu Y-X (2020) lncRNA H19 sponging miR-93 to regulate inflammation in retinal epithelial cells under hyperglycemia via XBP1s. Inflamm Res 69(3):255–265

    Article  CAS  PubMed  Google Scholar 

  89. Zha T, Su F, Liu X, Yang C, Liu L (2019) Role of long non-coding RNA (LncRNA) LINC-PINT downregulation in cardiomyopathy and retinopathy progression among patients with type 2 diabetes. Med Sci Monit 25:8509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ke N, Pi L-H, Liu Q, Chen L (2019) Long noncoding RNA SNHG7 inhibits high glucose-induced human retinal endothelial cells angiogenesis by regulating miR-543/SIRT1 axis. Biochem Biophys Res Commun 514(2):503–509

    Article  CAS  PubMed  Google Scholar 

  91. Yu W, Zhao G-q, Cao R-j, Zhu Z-h, Li K (2017) LncRNA NONRATT021972 was associated with neuropathic pain scoring in patients with type 2 diabetes. Behav Neurol. https://doi.org/10.1155/2017/2941297

    Article  PubMed  PubMed Central  Google Scholar 

  92. Peng H, Zou L, Xie J, Wu H, Wu B, Zhu G, Lv Q, Zhang X, Liu S, Li G (2017) LncRNA NONRATT021972 siRNA decreases diabetic neuropathic pain mediated by the P2X 3 receptor in dorsal root ganglia. Mol Neurobiol 54(1):511–523

    Article  CAS  PubMed  Google Scholar 

  93. Wang S, Xu H, Zou L, Xie J, Wu H, Wu B, Yi Z, Lv Q, Zhang X, Ying M (2016) LncRNA uc. 48+ is involved in diabetic neuropathic pain mediated by the P2X 3 receptor in the dorsal root ganglia. Purinergic Signalling 12(1):139–148

    Article  CAS  PubMed  Google Scholar 

  94. Liu S, Zou L, Xie J, Xie W, Wen S, Xie Q, Gao Y, Li G, Zhang C, Xu C (2016) LncRNA NONRATT021972 siRNA regulates neuropathic pain behaviors in type 2 diabetic rats through the P2X 7 receptor in dorsal root ganglia. Mol Brain 9(1):1–13

    Article  CAS  Google Scholar 

  95. Liu C, Tao J, Wu H, Yang Y, Chen Q, Deng Z, Liu J, Xu C (2017) Effects of LncRNA BC168687 siRNA on diabetic neuropathic pain mediated by P2X7 receptor on SGCs in DRG of rats. BioMed Res Int. https://doi.org/10.1155/2017/7831251

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wu B, Zhang C, Zou L, Ma Y, Huang K, Lv Q, Zhang X, Wang S, Xue Y, Yi Z (2016) LncRNA uc. 48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats mediated by P2X7 receptor in SCG. Auton Neurosci 197:14–18

    Article  CAS  PubMed  Google Scholar 

  97. Tao S-C, Rui B-Y, Wang Q-Y, Zhou D, Zhang Y, Guo S-C (2018) Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds. Drug Delivery 25(1):241–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Guo J-R, Yin L, Chen Y-Q, Jin X-J, Zhou X, Zhu N-N, Liu X-Q, Wei H-W, Duan L-S (2018) Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway. Cell Commun Signal 16(1):84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Liu X-Q, Duan L-S, Chen Y-Q, Jin X-J, Zhu N-N, Zhou X, Wei H-W, Yin L, Guo J-R (2019) lncRNA MALAT1 accelerates wound healing of diabetic mice transfused with modified autologous blood via the HIF-1α signaling pathway. Molecular Therapy-Nucleic Acids 17:504–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Zhu L, Zhong Q, Yang T, Xiao X (2019) Improved therapeutic effects on diabetic foot by human mesenchymal stem cells expressing MALAT1 as a sponge for microRNA-205-5p. Aging (Albany NY) 11(24):12236

    Article  CAS  Google Scholar 

  101. Jia G, Hill MA, Sowers JR (2018) Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 122(4):624–638. https://doi.org/10.1161/circresaha.117.311586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Yang F, Qin Y, Wang Y, Li A, Lv J, Sun X, Che H, Han T, Meng S, Bai Y (2018) LncRNA KCNQ1OT1 mediates pyroptosis in diabetic cardiomyopathy. Cell Physiol Biochem 50(4):1230–1244

    Article  CAS  PubMed  Google Scholar 

  103. Chen Y, Tan S, Liu M, Li J (2018) LncRNA TINCR is downregulated in diabetic cardiomyopathy and relates to cardiomyocyte apoptosis. Scand Cardiovasc J 52(6):335–339

    Article  CAS  PubMed  Google Scholar 

  104. Li X, Wang H, Yao B, Xu W, Chen J, Zhou X (2016) lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy. Sci Rep 6:36340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Zhuo C, Jiang R, Lin X, Shao M (2017) LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy. Oncotarget 8(1):1429

    Article  PubMed  Google Scholar 

  106. Qi K, Zhong J (2018) LncRNA HOTAIR improves diabetic cardiomyopathy by increasing viability of cardiomyocytes through activation of the PI3K/Akt pathway. Exp Ther Med 16(6):4817–4823

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Chen K, Ma Y, Wu S, Zhuang Y, Liu X, Lv L, Zhang G (2019) Construction and analysis of a lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in diabetic cardiomyopathy. Mol Med Rep 20(2):1393–1403

    CAS  PubMed  Google Scholar 

  108. Zhou X, Zhang W, Jin M, Chen J, Xu W, Kong X (2017) lncRNA MIAT functions as a competing endogenous RNA to upregulate DAPK2 by sponging miR-22-3p in diabetic cardiomyopathy. Cell Death Dis 8(7):e2929–e2929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chen Y, Zhang Z, Zhu D, Zhao W, Li F (2019) Long non-coding RNA MEG3 serves as a ceRNA for microRNA-145 to induce apoptosis of AC16 cardiomyocytes under high glucose condition. Biosci Rep. https://doi.org/10.1042/BSR20190444

  110. Ren S, Zhang Y, Li B, Bu K, Wu L, Lu Y, Lu Y, Qiu Y (2019) Downregulation of lncRNA-SRA participates in the development of cardiovascular disease in type II diabetic patients. Exp Ther Med 17(5):3367–3372

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Zhang L, Wang Y-M (2019) Expression and function of lncRNA ANRIL in a mouse model of acute myocardial infarction combined with type 2 diabetes mellitus. J Chin Med Assoc 82(9):685–692

    Article  PubMed  Google Scholar 

  112. Xu H, Liu C, Rao S, He L, Zhang T, Sun S, Wu B, Zou L, Wang S, Xue Y (2016) LncRNA NONRATT021972 siRNA rescued decreased heart rate variability in diabetic rats in superior cervical ganglia. Auton Neurosci 201:1–7

    Article  CAS  PubMed  Google Scholar 

  113. Cherng Y-G, Tsai C-C, Chung H-H, Lai Y-W, Kuo S-C, Cheng J-T (2013) Antihyperglycemic action of sinapic acid in diabetic rats. J Agric Food Chem 61(49):12053–12059

    Article  CAS  PubMed  Google Scholar 

  114. Han Y, Qiu H, Pei X, Fan Y, Tian H, Geng J (2018) Low-dose sinapic acid abates the pyroptosis of macrophages by downregulation of lncRNA-MALAT1 in rats with diabetic atherosclerosis. J Cardiovasc Pharmacol 71(2):104–112

    Article  CAS  PubMed  Google Scholar 

  115. Janssen J, Lamberts S (2000) Circulating IGF-I and its protective role in the pathogenesis of diabetic angiopathy. J Peripher Nerv Syst 5(2):119–119

    Article  Google Scholar 

  116. Zhao Z, Liu B, Li B, Song C, Diao H, Guo Z, Li Z, Zhang J (2017) Inhibition of long noncoding RNA IGF2AS promotes angiogenesis in type 2 diabetes. Biomed Pharmacother 92:445–450

    Article  CAS  PubMed  Google Scholar 

  117. Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246

    Article  CAS  PubMed  Google Scholar 

  118. Reddy MA, Chen Z, Park JT, Wang M, Lanting L, Zhang Q, Bhatt K, Leung A, Wu X, Putta S (2014) Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA. Diabetes 63(12):4249–4261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wu H, Wen F, Jiang M, Liu Q, Nie Y (2018) LncRNA uc. 48+ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264. 7 macrophages. Int J Mole Med 42(2):1152–1160

    CAS  Google Scholar 

  120. Das S, Reddy MA, Senapati P, Stapleton K, Lanting L, Wang M, Amaram V, Ganguly R, Zhang L, Devaraj S (2018) Diabetes mellitus-induced long noncoding rna dnm3os regulates macrophage functions and inflammation via nuclear mechanisms. Arterioscler Thromb Vasc Biol 38(8):1806–1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wang L-Q, Zhou H-J (2018) LncRNA MALAT1 promotes high glucose-induced inflammatory response of microglial cells via provoking MyD88/IRAK1/TRAF6 signaling. Sci Rep 8(1):1–9

    Google Scholar 

  122. Kong X, Liu C-x, Wang G-d, Yang H, Yao X-m, Hua Q, Li X-y, Zhang H-m, Ma M-z, Su Q (2019) lncRNA LEGLTBC functions as a ceRNA to antagonize the effects of miR-34a on the downregulation of SIRT1 in glucolipotoxicity-induced INS-1 beta cell oxidative stress and apoptosis. Oxi Med Cell longev. https://doi.org/10.1155/2019/4010764

    Article  Google Scholar 

  123. Li P, Zhang N, Ping F, Gao Y, Cao L (2019) lncRNA SCAL1 inhibits inducible nitric oxide synthase in lung cells under high-glucose conditions. Exp Ther Med 18(3):1831–1836

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Zhang Y, Wu H, Wang F, Ye M, Zhu H, Bu S (2018) Long non-coding RNA MALAT 1 expression in patients with gestational diabetes mellitus. Int J Gynecol Obstet 140(2):164–169

    Article  CAS  Google Scholar 

  125. Shi Z, Zhao C, Long W, Ding H, Shen R (2015) Microarray expression profile analysis of long non-coding RNAs in umbilical cord plasma reveals their potential role in gestational diabetes-induced macrosomia. Cell Physiol Biochem 36(2):542–554

    Article  CAS  PubMed  Google Scholar 

  126. Lu J, Wu J, Zhao Z, Wang J, Chen Z (2018) Circulating LncRNA serve as fingerprint for gestational diabetes mellitus associated with risk of macrosomia. Cell Physiol Biochem 48(3):1012–1018

    Article  CAS  PubMed  Google Scholar 

  127. Ye H, Yang S, Zhang Y (2018) MEG3 damages fetal endothelial function induced by gestational diabetes mellitus via AKT pathway. Eur Rev Med Pharmacol Sci 22(24):8553–8560

    PubMed  Google Scholar 

  128. Zhang H (2019) Mechanism associated with aberrant lncRNA MEG3 expression in gestational diabetes mellitus. Exp Ther Med 18(5):3699–3706

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Wang Q, Lu X, Li C, Zhang W, Lv Y, Wang L, Wu L, Meng L, Fan Y, Ding H (2019) Down-regulated long non-coding RNA PVT1 contributes to gestational diabetes mellitus and preeclampsia via regulation of human trophoblast cells. Biomed Pharmacother 120:109501

    Article  CAS  PubMed  Google Scholar 

  130. Carter G, Miladinovic B, Patel AA, Deland L, Mastorides S, Patel NA (2015) Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus. BBA Clin 4:102–107

    Article  PubMed  PubMed Central  Google Scholar 

  131. Qi M, Zhou Q, Zeng W, Shen M, Liu X, Luo C, Long J, Chen W, Yan S, Zhang J (2017) Analysis of long non-coding RNA expression of lymphatic endothelial cells in response to type 2 diabetes. Cell Physiol Biochem 41(2):466–474

    Article  CAS  PubMed  Google Scholar 

  132. Wang X, Chang X, Zhang P, Fan L, Zhou T, Sun K (2017) Aberrant expression of long non-coding RNAs in newly diagnosed type 2 diabetes indicates potential roles in chronic inflammation and insulin resistance. Cell Physiol Biochem 43(6):2367–2378

    Article  CAS  PubMed  Google Scholar 

  133. Li X, Zhao Z, Gao C, Rao L, Hao P, Jian D, Li W, Tang H, Li M (2017) The diagnostic value of whole blood lncRNA ENST00000550337 1 for pre-diabetes and type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 125(06):377–383

    Article  CAS  PubMed  Google Scholar 

  134. Mansoori Z, Ghaedi H, Sadatamini M, Vahabpour R, Rahimipour A, Shanaki M, Kazerouni F (2018) Downregulation of long non-coding RNAs LINC00523 and LINC00994 in type 2 diabetes in an Iranian cohort. Mol Biol Rep 45(5):1227–1233

    Article  CAS  PubMed  Google Scholar 

  135. Ghaedi H, Sadatamini M, Vahabpour R, Rahimipour A, Shanaki M, Mansoori Z, Kazerouni F (2018) Long non-coding RNA LY86-AS1 and HCG27_201 expression in type 2 diabetes mellitus. Mol Biol Rep 45(6):2601–2608

    Article  PubMed  CAS  Google Scholar 

  136. de Gonzalo-Calvo D, Kenneweg F, Bang C, Toro R, Van Der Meer R, Rijzewijk L, Smit J, Lamb H, Llorente-Cortes V, Thum T (2016) Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes. Sci Rep 6(1):1–12

    CAS  Google Scholar 

  137. Zhao C, Hu J, Wang Z, Cao Z-Y, Wang L (2020) Serum LncRNA PANDAR may act as a novel serum biomarker of diabetic nephropathy in patients with type 2 diabetes. Clin Lab. https://doi.org/10.7754/Clin.Lab.2019.191032

    Article  PubMed  Google Scholar 

  138. Anbari DM (2020) Al-Harithy RN (2020) Ghrelin intronic lncRNAs, lnc-GHRL-3: 2 and lnc-GHRL-3: 3, as novel biomarkers in type 2 diabetes mellitus. Arch Physiol Biochem. https://doi.org/10.1080/13813455.2020.1817095

    Article  PubMed  Google Scholar 

  139. Saleh AA, Kasem HE, Zahran ES, El-Hefnawy SM (2020) Cell-free long non-coding RNAs (LY86-AS1 & HCG27_201and GAS5) as biomarkers for pre-diabetes and type 2 DM in Egypt. Biochem Biophys Rep 23:100770

    PubMed  PubMed Central  Google Scholar 

  140. Hu W, Ding Y, Wang S, Xu L, Yu H (2020) The construction and analysis of the aberrant lncRNA-miRNA-mRNA network in adipose tissue from type 2 diabetes individuals with obesity. J Diabetes Res. https://doi.org/10.1155/2020/3980742

    Article  PubMed  PubMed Central  Google Scholar 

  141. Gernapudi R, Wolfson B, Zhang Y, Yao Y, Yang P, Asahara H, Zhou Q (2016) MicroRNA 140 promotes expression of long noncoding RNA NEAT1 in adipogenesis. Mol Cell Biol 36(1):30–38

    Article  CAS  PubMed  Google Scholar 

  142. Liu Y, Wang Y, He X, Zhang S, Wang K, Wu H, Chen L (2018) LncRNA TINCR/miR-31-5p/C/EBP-α feedback loop modulates the adipogenic differentiation process in human adipose tissue-derived mesenchymal stem cells. Stem Cell Res 32:35–42

    Article  CAS  PubMed  Google Scholar 

  143. Divoux A, Karastergiou K, Xie H, Guo W, Perera RJ, Fried SK, Smith SR (2014) Identification of a novel lncRNA in gluteal adipose tissue and evidence for its positive effect on preadipocyte differentiation. Obesity 22(8):1781–1785

    Article  CAS  PubMed  Google Scholar 

  144. Wei S, Du M, Jiang Z, Hausman GJ, Zhang L, Dodson MV (2016) Long noncoding RNAs in regulating adipogenesis: new RNAs shed lights on obesity. Cell Mol Life Sci 73(10):2079–2087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Hui You L, Jun Zhu L, Yang L, Mei Shi C, Xia Pang L, Zhang J, Wei Cui X, Bo Ji C, Rong Guo X (2015) Transcriptome analysis reveals the potential contribution of long noncoding RNAs to brown adipocyte differentiation. Mole Genet Genomics 290(5):1659–1671

    Article  CAS  Google Scholar 

  146. Ma F, Li W, Tang R, Liu Z, Ouyang S, Cao D, Li Y, Wu J (2017) Long non-coding rna expression profiling in obesity mice with folic acid supplement. Cell Physiol Biochem 42(1):416–426. https://doi.org/10.1159/000477486

    Article  CAS  PubMed  Google Scholar 

  147. Li P, Chen X, Chang X, Tang T, Qi K (2020) A preliminary study on the differential expression of long noncoding RNAs and messenger RNAs in obese and control mice. J Cell Biochem 121(2):1126–1143

    Article  CAS  PubMed  Google Scholar 

  148. Virtue S (1801) Vidal-Puig A (2010) Adipose tissue expandability, lipotoxicity and the metabolic syndrome—an allostatic perspective. Biochem Biophys Acta 3:338–349

    Google Scholar 

  149. Oger F, Dubois-Chevalier J, Gheeraert C, Avner S, Durand E, Froguel P, Salbert G, Staels B, Lefebvre P, Eeckhoute J (2014) Peroxisome proliferator-activated receptor γ regulates genes involved in insulin/insulin-like growth factor signaling and lipid metabolism during adipogenesis through functionally distinct enhancer classes. J Biol Chem 289(2):708–722

    Article  CAS  PubMed  Google Scholar 

  150. Tang QQ, Lane MD (2012) Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem 81:715–736

    Article  CAS  PubMed  Google Scholar 

  151. Firmin FF, Oger F, Gheeraert C, Dubois-Chevalier J, Vercoutter-Edouart A-S, Alzaid F, Mazuy C, Dehondt H, Alexandre J, Derudas B (2017) The RBM14/CoAA-interacting, long intergenic non-coding RNA Paral1 regulates adipogenesis and coactivates the nuclear receptor PPARγ. Sci Rep 7(1):1–16

    Article  CAS  Google Scholar 

  152. Chen J, Liu Y, Lu S, Yin L, Zong C, Cui S, Qin D, Yang Y, Guan Q, Li X (2017) The role and possible mechanism of lncRNA U90926 in modulating 3T3-L1 preadipocyte differentiation. Int J Obes 41(2):299–308

    Article  CAS  Google Scholar 

  153. Liu W, Ma C, Yang B, Yin C, Zhang B, Xiao Y (2017) LncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice. Biochem Biophys Res Commun 493(3):1168–1175

    Article  CAS  PubMed  Google Scholar 

  154. Liu Y, Ji Y, Li M, Wang M, Yi X, Yin C, Wang S, Zhang M, Zhao Z, Xiao Y (2018) Integrated analysis of long noncoding RNA and mRNA expression profile in children with obesity by microarray analysis. Sci Rep 8(1):1–13

    Google Scholar 

  155. Chen R, Xin G, Zhang X (2019) Long non-coding RNA HCP5 serves as a ceRNA sponging miR-17-5p and miR-27a/b to regulate the pathogenesis of childhood obesity via the MAPK signaling pathway. J Pediatr Endocrinol Metab 32(12):1327–1339

    Article  CAS  PubMed  Google Scholar 

  156. Yang H, Liu P, Zhang J, Peng X, Lu Z, Yu S, Meng Y, Tong W, Chen J (2016) Long noncoding RNA MIR31HG exhibits oncogenic property in pancreatic ductal adenocarcinoma and is negatively regulated by miR-193b. Oncogene 35(28):3647–3657

    Article  CAS  PubMed  Google Scholar 

  157. Nie F-q, Ma S, Xie M, Liu Y-w, De W, Liu X-h (2016) Decreased long noncoding RNA MIR31HG is correlated with poor prognosis and contributes to cell proliferation in gastric cancer. Tumor Biol 37(6):7693–7701

    Article  CAS  Google Scholar 

  158. Montes M, Nielsen MM, Maglieri G, Jacobsen A, Højfeldt J, Agrawal-Singh S, Hansen K, Helin K, Van De Werken HJ, Pedersen JS (2015) The lncRNA MIR31HG regulates p16 INK4A expression to modulate senescence. Nat Commun 6(1):1–15

    Article  CAS  Google Scholar 

  159. Huang Y, Jin C, Zheng Y, Li X, Zhang S, Zhang Y, Jia L, Li W (2017) Knockdown of lncRNA MIR31HG inhibits adipocyte differentiation of human adipose-derived stem cells via histone modification of FABP4. Sci Rep 7(1):1–13

    CAS  Google Scholar 

  160. Li N, Hébert S, Song J, Kleinman CL, Richard S (2017) Transcriptome profiling in preadipocytes identifies long noncoding RNAs as Sam68 targets. Oncotarget 8(47):81994

    Article  PubMed  PubMed Central  Google Scholar 

  161. Karastergiou K, Smith SR, Greenberg AS, Fried SK (2012) Sex differences in human adipose tissues–the biology of pear shape. Biol Sex Differ 3(1):13

    Article  PubMed  PubMed Central  Google Scholar 

  162. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L (2005) Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study. Lancet 366(9497):1640–1649

    Article  PubMed  Google Scholar 

  163. Liu H, Li H, Jin L, Li G, Hu S, Ning C, Guo J, Shuai S, Li X, Li M (2018) Long noncoding RNA GAS5 suppresses 3T3-L1 cells adipogenesis through miR-21a-5p/PTEN signal pathway. DNA Cell Biol 37(9):767–777

    Article  CAS  PubMed  Google Scholar 

  164. Gesta S, Tseng Y-H, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131(2):242–256

    Article  CAS  PubMed  Google Scholar 

  165. Saely CH, Geiger K, Drexel H (2012) Brown versus white adipose tissue: a mini-review. Gerontology 58(1):15–23

    Article  PubMed  Google Scholar 

  166. You L, Zhou Y, Cui X, Wang X, Sun Y, Gao Y, Wang X, Wen J, Xie K, Tang R (2018) GM13133 is a negative regulator in mouse white adipocytes differentiation and drives the characteristics of brown adipocytes. J Cell Physiol 233(1):313–324

    Article  CAS  PubMed  Google Scholar 

  167. Zhao X-Y, Li S, Wang G-X, Yu Q, Lin JD (2014) A long noncoding RNA transcriptional regulatory circuit drives thermogenic adipocyte differentiation. Mol Cell 55(3):372–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Schmidt E, Dhaouadi I, Gaziano I, Oliverio M, Klemm P, Awazawa M, Mitterer G, Fernandez-Rebollo E, Pradas-Juni M, Wagner W (2018) LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat. Nat Commun 9(1):1–16

    Article  CAS  Google Scholar 

  169. Nuermaimaiti N, Liu J, Liang X, Jiao Y, Zhang D, Liu L, Meng X, Guan Y (2018) Effect of lncRNA HOXA11-AS1 on adipocyte differentiation in human adipose-derived stem cells. Biochem Biophys Res Commun 495(2):1878–1884. https://doi.org/10.1016/j.bbrc.2017.12.006

    Article  CAS  PubMed  Google Scholar 

  170. Iwase M, Sakai S, Seno S, Yeh Y-S, Kuo T, Takahashi H, Nomura W, Jheng H-F, Horton P, Osato N (2020) Long non-coding RNA 2310069B03Rik functions as a suppressor of Ucp1 expression under prolonged cold exposure in murine beige adipocytes. Biosci Biotechnol Biochem 84(2):305–313

    Article  CAS  PubMed  Google Scholar 

  171. Guo J, Zhou Y, Cheng Y, Fang W, Hu G, Wei J, Lin Y, Man Y, Guo L, Sun M (2018) Metformin-induced changes of the coding transcriptome and non-coding RNAs in the livers of non-alcoholic fatty liver disease mice. Cell Physiol Biochem 45(4):1487–1505

    Article  CAS  PubMed  Google Scholar 

  172. Wang X, Wang J (2018) High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3. Biol Chem 399(4):397–406

    Article  CAS  PubMed  Google Scholar 

  173. Chen Y, Huang H, Xu C, Yu C, Li Y (2017) Long non-coding RNA profiling in a non-alcoholic fatty liver disease rodent model: new insight into pathogenesis. Int J Mol Sci 18(1):21

    Article  PubMed Central  CAS  Google Scholar 

  174. Sookoian S, Rohr C, Salatino A, Dopazo H, Gianotti TF, Castaño GO, Pirola CJ (2017) Genetic variation in long noncoding RNAs and the risk of nonalcoholic fatty liver disease. Oncotarget 8(14):22917

    Article  PubMed  PubMed Central  Google Scholar 

  175. Chen X, Xu Y, Zhao D, Chen T, Gu C, Yu G, Chen K, Zhong Y, He J, Liu S (2018) LncRNA-AK012226 is involved in fat accumulation in db/db mice fatty liver and non-alcoholic fatty liver disease cell model. Front Pharmacol 9:888

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Li P, Ruan X, Yang L, Kiesewetter K, Zhao Y, Luo H, Chen Y, Gucek M, Zhu J, Cao H (2015) A liver-enriched long non-coding RNA, lncLSTR, regulates systemic lipid metabolism in mice. Cell Metab 21(3):455–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Chen G, Yu D, Nian X, Liu J, Koenig RJ, Xu B, Sheng L (2016) LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL). Sci Rep 6(1):1–13

    CAS  Google Scholar 

  178. Kammoun HL, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, Ferré P, Foufelle F (2009) GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest 119(5):1201–1215. https://doi.org/10.1172/jci37007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Zhang M, Chi X, Qu N, Wang C (2018) Long noncoding RNA lncARSR promotes hepatic lipogenesis via Akt/SREBP-1c pathway and contributes to the pathogenesis of nonalcoholic steatohepatitis. Biochem Biophys Res Commun 499(1):66–70

    Article  CAS  PubMed  Google Scholar 

  180. Brown MS, Radhakrishnan A, Goldstein JL (2018) Retrospective on cholesterol homeostasis: the central role of scap. Annu Rev Biochem 87:783–807

    Article  CAS  PubMed  Google Scholar 

  181. Calkin AC, Tontonoz P (2012) Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat Rev Mol Cell Biol 13(4):213–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Zhao X-Y, Xiong X, Liu T, Mi L, Peng X, Rui C, Guo L, Li S, Li X, Lin JD (2018) Long noncoding RNA licensing of obesity-linked hepatic lipogenesis and NAFLD pathogenesis. Nat Commun 9(1):1–14

    Article  CAS  Google Scholar 

  183. VerHague MA, Cheng D, Weinberg RB, Shelness GS (2013) Apolipoprotein A-IV expression in mouse liver enhances triglyceride secretion and reduces hepatic lipid content by promoting very low density lipoprotein particle expansion. Arterioscler Thromb Vasc Biol 33(11):2501–2508

    Article  CAS  PubMed  Google Scholar 

  184. Wang F, Kohan AB, Kindel TL, Corbin KL, Nunemaker CS, Obici S, Woods SC, Davidson WS, Tso P (2012) Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion. Proc Natl Acad Sci 109(24):9641–9646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Qin W, Li X, Xie L, Li S, Liu J, Jia L, Dong X, Ren X, Xiao J, Yang C (2016) A long non-coding RNA, APOA4-AS, regulates APOA4 expression depending on HuR in mice. Nucleic Acids Res 44(13):6423–6433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Guo J, Fang W, Sun L, Lu Y, Dou L, Huang X, Tang W, Yu L, Li J (2018) Ultraconserved element uc. 372 drives hepatic lipid accumulation by suppressing miR-195/miR4668 maturation. Nat Commun 9(1):1–15

    CAS  Google Scholar 

  187. Luo P, Qin C, Zhu L, Fang C, Zhang Y, Zhang H, Pei F, Tian S, Zhu XY, Gong J (2018) Ubiquitin-specific peptidase 10 (USP10) inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6. Hepatology 68(5):1786–1803

    Article  CAS  PubMed  Google Scholar 

  188. Sun Y, Song Y, Liu C, Geng J (2019) LncRNA NEAT1-MicroRNA-140 axis exacerbates nonalcoholic fatty liver through interrupting AMPK/SREBP-1 signaling. Biochem Biophys Res Commun 516(2):584–590

    Article  CAS  PubMed  Google Scholar 

  189. Wang X (2018) Down-regulation of lncRNA-NEAT1 alleviated the non-alcoholic fatty liver disease via mTOR/S6K1 signaling pathway. J Cell Biochem 119(2):1567–1574

    Article  CAS  PubMed  Google Scholar 

  190. Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T, Koike K, Tsuzaki R, Matsumoto K, Miyake Y (2012) Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology 56(3):912–921

    Article  CAS  PubMed  Google Scholar 

  191. Fu X, Zhu J, Zhang L, Shu J (2019) Long non-coding RNA NEAT1 promotes steatosis via enhancement of estrogen receptor alpha-mediated AQP7 expression in HepG2 cells. Artif Cells Nanomed Biotechnol 47(1):1782–1787

    Article  CAS  PubMed  Google Scholar 

  192. Du J, Niu X, Wang Y, Kong L, Wang R, Zhang Y, Zhao S, Nan Y (2015) MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a. Sci Rep 5(1):1–14

    Article  Google Scholar 

  193. Latorre J, Moreno-Navarrete J, Mercader J, Sabater M, Rovira O, Gironès J, Ricart W, Fernandez-Real J, Ortega F (2017) Decreased lipid metabolism but increased FA biosynthesis are coupled with changes in liver microRNAs in obese subjects with NAFLD. Int J Obes 41(4):620–630

    Article  CAS  Google Scholar 

  194. Chen X, Tan X-R, Li S-J, Zhang X-X (2019) LncRNA NEAT1 promotes hepatic lipid accumulation via regulating miR-146a-5p/ROCK1 in nonalcoholic fatty liver disease. Life Sci 235:116829

    Article  CAS  PubMed  Google Scholar 

  195. Atanasovska B, Rensen SS, van der Sijde MR, Marsman G, Kumar V, Jonkers I, Withoff S, Shiri-Sverdlov R, Greve JWM, Faber KN (2017) A liver-specific long noncoding RNA with a role in cell viability is elevated in human nonalcoholic steatohepatitis. Hepatology 66(3):794–808

    Article  CAS  PubMed  Google Scholar 

  196. Shen X, Guo H, Xu J, Wang J (2019) Inhibition of lncRNA HULC improves hepatic fibrosis and hepatocyte apoptosis by inhibiting the MAPK signaling pathway in rats with nonalcoholic fatty liver disease. J Cell Physiol 234(10):18169–18179

    Article  CAS  PubMed  Google Scholar 

  197. Huang P, Huang F-z, Liu H-z, Zhang T-y, Yang M-s, Sun C-z (2019) LncRNA MEG3 functions as a ceRNA in regulating hepatic lipogenesis by competitively binding to miR-21 with LRP6. Metabolism 94:1–8

    Article  PubMed  CAS  Google Scholar 

  198. Ma T-t, Huang C, Ni Y, Yang Y, Li J (2018) ATP citrate lyase and LncRNA NONMMUT010685 play crucial role in nonalcoholic fatty liver disease based on analysis of microarray data. Cell Physiol Biochem 51(2):871–885

    Article  CAS  PubMed  Google Scholar 

  199. Chen Y, Chen X, Gao J, Xu C, Xu P, Li Y, Zhu Y, Yu C (2019) Long noncoding RNA FLRL2 alleviated nonalcoholic fatty liver disease through Arntl-Sirt1 pathway. FASEB J 33(10):11411–11419

    Article  CAS  PubMed  Google Scholar 

  200. Zhang J, Cao H, Zhang B, Cao H, Xu X, Ruan H, Yi T, Tan L, Qu R, Song G (2013) Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling. J Cell Mol Med 17(11):1484–1493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Yuan X, Wang J, Tang X, Li Y, Xia P, Gao X (2015) Berberine ameliorates nonalcoholic fatty liver disease by a global modulation of hepatic mRNA and lncRNA expression profiles. J Transl Med 13(1):1–11

    Article  CAS  Google Scholar 

  202. Asrani SK, Devarbhavi H, Eaton J, Kamath PS (2019) Burden of liver diseases in the world. J Hepatol 70(1):151–171

    Article  PubMed  Google Scholar 

  203. Zhang C-Y, Yuan W-G, He P, Lei J-H, Wang C-X (2016) Liver fibrosis and hepatic stellate cells: etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 22(48):10512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Zhou B, Yuan W, Li X (2018) LncRNA Gm5091 alleviates alcoholic hepatic fibrosis by sponging miR-27b/23b/24 in mice. Cell Biol Int 42(10):1330–1339. https://doi.org/10.1002/cbin.11021

    Article  CAS  PubMed  Google Scholar 

  205. Tu X, Zhang Y, Zheng X, Deng J, Li H, Kang Z, Cao Z, Huang Z, Ding Z, Dong L (2017) TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice. Sci Rep 7(1):1–14

    Article  CAS  Google Scholar 

  206. Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, Kawada N (2012) MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut 61(11):1600–1609

    Article  CAS  PubMed  Google Scholar 

  207. Yu F, Zheng J, Mao Y, Dong P, Lu Z, Li G, Guo C, Liu Z, Fan X (2015) Long non-coding RNA growth arrest-specific transcript 5 (GAS5) inhibits liver fibrogenesis through a mechanism of competing endogenous RNA. J Biol Chem 290(47):28286–28298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Liu X-Y, He Y-J, Yang Q-H, Huang W, Liu Z-H, Ye G-R, Tang S-H, Shu J-C (2015) Induction of autophagy and apoptosis by miR-148a through the sonic hedgehog signaling pathway in hepatic stellate cells. Am J Cancer Res 5(9):2569

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Li Z, Wang J, Zeng Q, Hu C, Zhang J, Wang H, Yan J, Li H, Yu Z (2018) Long noncoding RNA HOTTIP promotes mouse hepatic stellate cell activation via downregulating miR-148a. Cell Physiol Biochem 51(6):2814–2828. https://doi.org/10.1159/000496012

    Article  CAS  PubMed  Google Scholar 

  210. Zhu J, Luo Z, Pan Y, Zheng W, Li W, Zhang Z, Xiong P, Xu D, Du M, Wang B, Yu J, Zhang J, Liu J (2019) H19/miR-148a/USP4 axis facilitates liver fibrosis by enhancing TGF-β signaling in both hepatic stellate cells and hepatocytes. J Cell Physiol 234(6):9698–9710. https://doi.org/10.1002/jcp.27656

    Article  CAS  PubMed  Google Scholar 

  211. Cerase A, Tartaglia GG (2020) Long non-coding RNA-polycomb intimate rendezvous. Open Biol 10(9):200126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Bian E-B, Wang Y-Y, Yang Y, Wu B-M, Xu T, Meng X-M, Huang C, Zhang L, Lv X-W, Xiong Z-G, Li J (2017) Hotair facilitates hepatic stellate cells activation and fibrogenesis in the liver. Biochem Biophys Acta 1863(3):674–686. https://doi.org/10.1016/j.bbadis.2016.12.009

    Article  CAS  Google Scholar 

  213. Lam AP, Gottardi CJ (2011) β-catenin signaling: a novel mediator of fibrosis and potential therapeutic target. Curr Opin Rheumatol 23(6):562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Yu F, Dong P, Mao Y, Zhao B, Huang Z, Zheng J (2019) Loss of lncRNA-SNHG7 promotes the suppression of hepatic stellate cell activation via miR-378a-3p and DVL2. Mol Ther Nucleic Acids 17:235–244. https://doi.org/10.1016/j.omtn.2019.05.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Han X, Hong Y, Zhang K (2018) TUG1 is involved in liver fibrosis and activation of HSCs by regulating miR-29b. Biochem Biophys Res Commun 503(3):1394–1400

    Article  CAS  PubMed  Google Scholar 

  216. Wang J, Chu ES, Chen H-Y, Man K, Go MY, Huang XR, Lan HY, Sung JJ, Yu J (2015) microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway. Oncotarget 6(9):7325

    Article  PubMed  Google Scholar 

  217. Yu F, Chen B, Dong P, Zheng J (2017) HOTAIR epigenetically modulates PTEN expression via MicroRNA-29b: a novel mechanism in regulation of liver fibrosis. Mol Ther 25(1):205–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Yang J-J, Tao H, Li J (2014) Hedgehog signaling pathway as key player in liver fibrosis: new insights and perspectives. Expert Opin Ther Targets 18(9):1011–1021. https://doi.org/10.1517/14728222.2014.927443

    Article  CAS  PubMed  Google Scholar 

  219. Yu F, Lu Z, Chen B, Wu X, Dong P, Zheng J (2015) Salvianolic acid B-induced micro RNA-152 inhibits liver fibrosis by attenuating DNMT 1-mediated Patched1 methylation. J Cell Mol Med 19(11):2617–2632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Zheng J, Yu F, Dong P, Wu L, Zhang Y, Hu Y, Zheng L (2016) Long non-coding RNA PVT1 activates hepatic stellate cells through competitively binding microRNA-152. Oncotarget 7(39):62886

    Article  PubMed  PubMed Central  Google Scholar 

  221. Bae JS, Kim JH, Pasaje CF, Cheong HS, Lee TH, Koh IS, Lee HS, Kim YJ, Shin HD (2012) Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver diseases. Dig Liver Dis 44(10):849–854. https://doi.org/10.1016/j.dld.2012.04.021

    Article  CAS  PubMed  Google Scholar 

  222. Yu F, Lu Z, Cai J, Huang K, Chen B, Li G, Dong P, Zheng J (2015) MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis. Cell Cycle 14(24):3885–3896. https://doi.org/10.1080/15384101.2015.1120917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. He Y, Wu Y-T, Huang C, Meng X-M, Ma T-T, Wu B-M, Xu F-Y, Zhang L, Lv X-W, Li J (2014) Inhibitory effects of long noncoding RNA MEG3 on hepatic stellate cells activation and liver fibrogenesis. Biochem Biophys Acta 1842(11):2204–2215. https://doi.org/10.1016/j.bbadis.2014.08.015

    Article  CAS  PubMed  Google Scholar 

  224. Chen L, Zhang Q, Yu C, Wang F, Kong X (2020) Functional roles of CCL5/RANTES in liver disease. Liver Res 4(1):28–34. https://doi.org/10.1016/j.livres.2020.01.002

    Article  Google Scholar 

  225. Leti F, Legendre C, Still CD, Chu X, Petrick A, Gerhard GS, DiStefano JK (2017) Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells. Transl Res 190:25-39.e21. https://doi.org/10.1016/j.trsl.2017.09.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Yu F, Zheng J, Mao Y, Dong P, Li G, Lu Z, Guo C, Liu Z, Fan X (2015) Long non-coding RNA APTR promotes the activation of hepatic stellate cells and the progression of liver fibrosis. Biochem Biophys Res Commun 463(4):679–685. https://doi.org/10.1016/j.bbrc.2015.05.124

    Article  CAS  PubMed  Google Scholar 

  227. Jeong SW, Jang JY, Lee SH, Kim SG, Cheon YK, Kim YS, Cho YD, Kim HS, Lee JS, Jin S-Y (2010) Increased expression of cyclooxygenase-2 is associated with the progression to cirrhosis. Korean J Intern Med 25(4):364

    Article  PubMed  PubMed Central  Google Scholar 

  228. Tang SH, Gao JH, Wen SL, Tong H, Yan ZP, Liu R, Tang CW (2017) Expression of cyclooxygenase-2 is correlated with lncRNA-COX-2 in cirrhotic mice induced by carbon tetrachloride. Mol Med Rep 15(4):1507–1512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Khomich O, Ivanov AV, Bartosch B (2020) Metabolic hallmarks of hepatic stellate cells in liver fibrosis. Cells 9(1):24

    Article  CAS  Google Scholar 

  230. Zhang K, Han X, Zhang Z, Zheng L, Hu Z, Yao Q, Cui H, Shu G, Si M, Li C, Shi Z, Chen T, Han Y, Chang Y, Yao Z, Han T, Hong W (2017) The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFβ and Notch pathways. Nat Commun 8(1):144. https://doi.org/10.1038/s41467-017-00204-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Li L-J, Wu X-Y, Tan S-W, Xie Z-J, Pan X-M, Pan S-W, Bai W-R-N, Li H-J, Liu H-L, Jiang J (2019) Lnc-TCL6 is a potential biomarker for early diagnosis and grade in liver-cirrhosis patients. Gastroenterol Rep 7(6):434–443

    Article  Google Scholar 

  232. Duan L, Liu C, Hu J, Liu Y, Wang J, Chen G, Li Z, Chen H (2018) Epigenetic mechanisms in coronary artery disease: the current state and prospects. Trends Cardiovasc Med 28(5):311–319

    Article  CAS  PubMed  Google Scholar 

  233. Turner AW, Wong D, Khan MD, Dreisbach CN, Palmore M, Miller CL (2019) Multi-omics approaches to study long non-coding RNA function in atherosclerosis. Front Cardiovasc Med 6:9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Tabas I, García-Cardeña G, Owens GK (2015) Recent insights into the cellular biology of atherosclerosis. J Cell Biol 209(1):13–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Xu Y, Shao B (2018) Circulating lncRNA IFNG-AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in patients with coronary artery disease. J Clin Lab Anal 32(7):e22452

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  236. Alikhah A, Kakhki MP, Ahmadi A, Dehghanzad R, Boroumand MA, Behmanesh M (2018) The role of lnc-DC long non-coding RNA and SOCS1 in the regulation of STAT3 in coronary artery disease and type 2 diabetes mellitus. J Diabetes Complications 32(3):258–265

    Article  PubMed  Google Scholar 

  237. Wang X, Liu Q, Ihsan A, Huang L, Dai M, Hao H, Cheng G, Liu Z, Wang Y, Yuan Z (2012) JAK/STAT pathway plays a critical role in the proinflammatory gene expression and apoptosis of RAW264. 7 cells induced by trichothecenes as DON and T-2 toxin. Toxicol Sci 127(2):412–424

    Article  CAS  PubMed  Google Scholar 

  238. Li L, Wang L, Li H, Han X, Chen S, Yang B, Hu Z, Zhu H, Cai C, Chen J (2018) Characterization of LncRNA expression profile and identification of novel LncRNA biomarkers to diagnose coronary artery disease. Atherosclerosis 275:359–367

    Article  CAS  PubMed  Google Scholar 

  239. Cai Y, Yang Y, Chen X, He D, Zhang X, Wen X, Hu J, Fu C, Qiu D, Jose PA (2016) Circulating “LncPPARδ” from monocytes as a novel biomarker for coronary artery diseases. Medicine 95(6):e2360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Lorenzon A, Calore M, Poloni G, De Windt LJ, Braghetta P, Rampazzo A (2017) Wnt/β-catenin pathway in arrhythmogenic cardiomyopathy. Oncotarget 8(36):60640

    Article  PubMed  PubMed Central  Google Scholar 

  241. Li X, Hou L, Cheng Z, Zhou S, Qi J, Cheng J (2019) Overexpression of GAS5 inhibits abnormal activation of Wnt/β-catenin signaling pathway in myocardial tissues of rats with coronary artery disease. J Cell Physiol 234(7):11348–11359

    Article  CAS  PubMed  Google Scholar 

  242. Hu Y-W, Guo F-X, Xu Y-J, Li P, Lu Z-F, McVey DG, Zheng L, Wang Q, John HY, Kang C-M (2019) Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN. J Clin Investig 129(3):1115–1128

    Article  PubMed  PubMed Central  Google Scholar 

  243. Pan J (2017) LncRNA H19 promotes atherosclerosis by regulating MAPK and NF-kB signaling pathway. Eur Rev Med Pharmacol Sci 21(2):322–328

    PubMed  Google Scholar 

  244. Liao B, Chen R, Lin F, Mai A, Chen J, Li H, Xu Z, Dong S (2018) Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway. J Cell Biochem 119(3):2797–2805

    Article  CAS  PubMed  Google Scholar 

  245. Wu Z, He Y, Li D, Fang X, Shang T, Zhang H, Zheng X (2017) Long noncoding RNA MEG3 suppressed endothelial cell proliferation and migration through regulating miR-21. Am J Transl Res 9(7):3326

    CAS  PubMed  PubMed Central  Google Scholar 

  246. Wang X, Zhao Z, Zhang W, Wang Y (2019) Long noncoding RNA LINC00968 promotes endothelial cell proliferation and migration via regulating miR-9-3p expression. J Cell Biochem 120(5):8214–8221

    Article  CAS  Google Scholar 

  247. Cho H, Shen G-Q, Wang X, Wang F, Archacki S, Li Y, Yu G, Chakrabarti S, Chen Q, Wang QK (2019) Long noncoding RNA ANRIL regulates endothelial cell activities associated with coronary artery disease by up-regulating CLIP1, EZR, and LYVE1 genes. J Biol Chem 294(11):3881–3898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Schonrock N, Harvey RP, Mattick JS (2012) Long noncoding RNAs in cardiac development and pathophysiology. Circ Res 111(10):1349–1362

    Article  CAS  PubMed  Google Scholar 

  249. Yin Q, Wu A, Liu M (2017) Plasma long non-coding RNA (lncRNA) GAS5 is a new biomarker for coronary artery disease. Med Sci Monit 23:6042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Yao Y, Xiong G, Jiang X, Song T (2019) The overexpression of lncRNA H19 as a diagnostic marker for coronary artery disease. Rev Assoc Med Bras 65(2):110–117

    Article  Google Scholar 

  251. Zhang Z, Gao W, Long Q-Q, Zhang J, Li Y-F, Yan J-J, Yang Z-J, Wang L-S (2017) Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Sci Rep 7(1):1–9

    CAS  Google Scholar 

  252. Bitarafan S, Yari M, Broumand MA, Ghaderian SMH, Rahimi M, Mirfakhraie R, Azizi F, Omrani MD (2019) Association of increased levels of lncRNA H19 in PBMCs with risk of coronary artery disease. Cell J (Yakhteh) 20(4):564

    Google Scholar 

  253. Cai Y, Yang Y, Chen X, Wu G, Zhang X, Liu Y, Yu J, Wang X, Fu J, Li C (2016) Circulating ‘lncRNA OTTHUMT00000387022’from monocytes as a novel biomarker for coronary artery disease. Cardiovasc Res 112(3):714–724

    Article  CAS  PubMed  Google Scholar 

  254. Avazpour N, Hajjari M, Yazdankhah S, Sahni A, Foroughmand AM (2018) Circulating HOTAIR LncRNA is potentially up-regulated in coronary artery disease. Genomics Inform 16(4):e25

    Article  PubMed  PubMed Central  Google Scholar 

  255. Yari M, Bitarafan S, Broumand MA, Fazeli Z, Rahimi M, Ghaderian SMH, Mirfakhraie R, Omrani MD (2018) Association between long noncoding RNA ANRIL expression variants and susceptibility to coronary artery disease. Int J Mole Cell Med 7(1):1

    CAS  Google Scholar 

  256. Shahmoradi N, Nasiri M, Kamfiroozi H, Kheiry MA (2017) Association of the rs555172 polymorphism in SENCR long non-coding RNA and atherosclerotic coronary artery disease. J Cardiovasc Thoracic Res 9(3):170

    Article  Google Scholar 

  257. Tang S-s, Cheng J, Cai M-y, Yang X-l, Liu X-g, Zheng B-y, Xiong X-d (2016) Association of lincRNA-p21 haplotype with coronary artery disease in a Chinese Han population. Dis Markers 2016:9109743

    PubMed  PubMed Central  Google Scholar 

  258. Wu C, Yan H, Sun J, Yang F, Song C, Jiang F, Li Y, Dong J, Zheng G-Y, Tian X-L (2013) NEXN is a novel susceptibility gene for coronary artery disease in Han Chinese. PLoS ONE 8(12):e82135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  259. Mangalarapu M, Vinukonda S, Komaravalli PL, Nagula P, Koduganti RR, Korripally P, Sagurthi SR (2019) Association of CDKN2BAS gene polymorphism with periodontitis and coronary artery disease from south Indian population. Gene 710:324–332

    Article  CAS  PubMed  Google Scholar 

  260. Gao W, Zhu M, Wang H, Zhao S, Zhao D, Yang Y, Wang Z-M, Wang F, Yang Z-J, Lu X (2015) Association of polymorphisms in long non-coding RNA H19 with coronary artery disease risk in a Chinese population. Mutation Res/Fundamental Mole Mech Mutagenesis 772:15–22

    Article  CAS  Google Scholar 

  261. Hu W, Ding H, Ouyang A, Zhang X, Xu Q, Han Y, Zhang X, Jin Y (2019) LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case–control study in a Chinese population. Biosci Rep. https://doi.org/10.1042/BSR20182213

  262. Wang G, Li Y, Peng Y, Tang J, Li H (2018) Association of polymorphisms in MALAT1 with risk of coronary atherosclerotic heart disease in a Chinese population. Lipids Health Dis 17(1):75

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  263. Xu B, Fang Z, He S, Wang J, Yang X (2018) ANRIL polymorphism rs4977574 is associated with increased risk of coronary artery disease in Asian populations: a meta-analysis of 12,005 subjects. Medicine 97(39):e12641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Hu L, Su G, Wang X (2019) The roles of ANRIL polymorphisms in coronary artery disease: a meta-analysis. Biosci Rep. https://doi.org/10.1042/BSR20181559

  265. Xu L-B, Zhang Y-Q, Zhang N-N, Li B, Weng J-Y, Li X-Y, Lu W-C, Yu P-R, Wang X, Li Y (2020) Rs10757274 gene polymorphisms in coronary artery disease: a systematic review and a meta-analysis. Medicine 99(3):e18841

    Article  PubMed  PubMed Central  Google Scholar 

  266. Shen Z, She Q (2018) Association between the deletion allele of ins/del polymorphism (rs145204276) in the promoter region of gas5 with the risk of atherosclerosis. Cell Physiol Biochem 49(4):1431–1443

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was financially supported by Abadan Faculty of Medical sciences, Abadan, Iran (Grant Number: 99T-952).

Author information

Authors and Affiliations

  1. Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran

    B. Alipoor

  2. Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran

    S. Nikouei

  3. Department of Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

    F. Rezaeinejad

  4. Abadan Faculty of Medical Sciences, Abadan, Iran

    S-N. Malakooti-Dehkordi & H. Ghasemi

  5. MSc student of Hematology, Student Research Committee, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

    Z. Sabati

Authors
  1. B. Alipoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Nikouei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Rezaeinejad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S-N. Malakooti-Dehkordi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Z. Sabati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. Ghasemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Ghasemi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Medical Ethics Committee of Abadan Faculty of Medical Sciences (IR. ABADANUMS.REC. 1399.171).

Informed consent

For this type of study informed consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alipoor, B., Nikouei, S., Rezaeinejad, F. et al. Long non-coding RNAs in metabolic disorders: pathogenetic relevance and potential biomarkers and therapeutic targets. J Endocrinol Invest 44, 2015–2041 (2021). https://doi.org/10.1007/s40618-021-01559-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-021-01559-8

Keywords

Search

Navigation