Skip to main content

Advertisement

SpringerLink
Log in

Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

The Long non-coding RNA (lncRNA) expression profile data of ten samples including human Mesenchymal Stem Cell (MSC) adipogenic differentiation 0, 3, and 6 days from the GEO database, and then perform gene ID conversion, BLAST comparison, and annotation marking. Finally, group A (treatment group on day 3 of differentiation and control group on day 0 of differentiation) obtained a total of 1180 mRNA and 185 lncRNA; group B (treatment group on day 6 of differentiation and control group on day 0 of differentiation). A total of 1376 mRNA and 206 lncRNA were obtained. Finally, we processed the differential lncRNAs and mRNAs obtained in the two groups, and obtained 113 shared differential lncRNAs to further predict the targeted miRNA, a total of 815 lncRNA-miRNA pairs. The targeted mRNA was further predicted, and the grouped differential mRNAs were combined to obtain 64 differential mRNAs. In the end, we obtained 216 ceRNAs containing 26 lncRNAs, 27 miRNAs and 64 mRNAs. We found that the mRNAs in the ceRNA network were mainly enriched with 45 Gene Ontology (GO) terms, mainly including glucose homeostasis mechanism and insulin stimulation response. 69 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were mainly enriched. It mainly includes many pathways related to lipid metabolism such as Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), Rap1, cAMP, mitogen-activated protein kinase (MAPK), Ras, hypoxia inducible factor-1 (HIF-1), PI3K-Akt, insulin signaling and so on. In the end, we identified 216 ceRNA regulatory relationships related to obesity research. Our research provides a clearer direction for understanding the molecular mechanism of obesity, the screening and determination of drug targets biomarkers in the future.

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
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All the data are available within the manuscript.

References

  • Agapito G (2019) Computer tools to analyze microarray data. Methods Mol Biol 1986:267–282

    Article  CAS  PubMed  Google Scholar 

  • Alonso-Betanzos A, Bolón-Canedo V, Morán-Fernández L, Sánchez-Maroño N (2019) A Review of microarray datasets: where to find them and specific characteristics. Methods Mol Biol 1986:65–85

    Article  CAS  PubMed  Google Scholar 

  • Behzadi P, Ranjbar R (2019) DNA microarray technology and bioinformatic web services. Acta Microbiol Immunol Hung 66(1):19–30

    Article  CAS  PubMed  Google Scholar 

  • Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA (2012) Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 51(5):277–304

    Article  CAS  PubMed  Google Scholar 

  • Cabiati M, Randazzo E, Salvadori C, Peroni D, Federico G, Del Ry S (2020) Circulating microRNAs associated with C-type natriuretic peptide in childhood obesity. Peptides 133:170387

    Article  CAS  PubMed  Google Scholar 

  • Cai C, Min S, Yan B, Liu W, Yang X, Li L, Wang T, Jin A (2019) MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling. Aging 11(16):6371–6384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen T, Zhang Y, Liu Y, Zhu D, Yu J, Li G, Sun Z, Wang W, Jiang H, Hong Z (2019) MiR-27a promotes insulin resistance and mediates glucose metabolism by targeting PPAR-γ-mediated PI3K/AKT signaling. Aging 11(18):7510–7524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox AJ, West NP, Cripps AW (2015) Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol 3(3):207–215

    Article  CAS  PubMed  Google Scholar 

  • Fachel AA, Tahira AC, Vilella-Arias SA, Maracaja-Coutinho V, Gimba ER, Vignal GM, Campos FS, Reis EM, Verjovski-Almeida S (2013) Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations. Mol Cancer 12(1):140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Font-Burgada J, Sun B, Karin M (2016) Obesity and cancer: the oil that feeds the flame. Cell Metab 23(1):48–62

    Article  CAS  PubMed  Google Scholar 

  • Friedman JM (2000) Obesity in the new millennium. Nature 404(6778):632–634

    Article  CAS  PubMed  Google Scholar 

  • Guo W, Jiang H, Li H, Li F, Yu Q, Liu Y, Jiang W, Zhang M (2019) LncRNA-SRA1 suppresses osteosarcoma cell proliferation while promoting cell apoptosis. Technol Cancer Res Treat 18:1533033819841438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, Zhang X, Huang W, Miao X (2017) Identification and characterization of differentially expressed miRNAs in subcutaneous adipose between Wagyu and Holstein cattle. Sci Rep 7:44026

    Article  PubMed  PubMed Central  Google Scholar 

  • Hsu SD, Tseng YT, Shrestha S, Lin YL, Khaleel A, Chou CH, Chu CF, Huang HY, Lin CM, Ho SY, Jian TY, Lin FM, Chang TH, Weng SL, Liao KW, Liao IE, Liu CC, Huang HD (2014) miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res 42:D78-85

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Chen HY, Yu CY, Xu J, Wang JL, Qian J, Zhang X, Fang JY (2014) A long non-coding RNA signature to improve prognosis prediction of colorectal cancer. Oncotarget 5(8):2230–2242

    Article  PubMed  PubMed Central  Google Scholar 

  • da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57

    Article  CAS  Google Scholar 

  • Huang S, Wang S, Bian C, Yang Z, Zhou H, Zeng Y, Li H, Han Q, Zhao RC (2012) Upregulation of miR-22 promotes osteogenic differentiation and inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by repressing HDAC6 protein expression. Stem Cells Dev 21(13):2531–2540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janderová L, McNeil M, Murrell AN, Mynatt RL, Smith SR (2003) Human mesenchymal stem cells as an in vitro model for human adipogenesis. Obes Res 11(1):65–74

    Article  PubMed  Google Scholar 

  • Jeggari A, Marks DS, Larsson E (2012) miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics 28(15):2062–2063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji L, Li X (2019) Long noncoding RNA MEG3 is a tumor suppressor in choriocarcinoma by upregulation of microRNA-211. J Cell Physiol 234(12):22911–22920

    Article  CAS  PubMed  Google Scholar 

  • Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20

    Article  CAS  PubMed  Google Scholar 

  • Li J, Chen Z, Tian L, Zhou C, He MY, Gao Y, Wang S, Zhou F, Shi S, Feng X, Sun N, Liu Z, Skogerboe G, Dong J, Yao R, Zhao Y, Sun J, Zhang B, Yu Y, Shi X, Luo M, Shao K, Li N, Qiu B, Tan F, Chen R, He J (2014) LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma. Gut 63(11):1700–1710

    Article  CAS  PubMed  Google Scholar 

  • Li M, Sun X, Cai H, Sun Y, Plath M, Li C, Lan X, Lei C, Lin F, Bai Y, Chen H (2016) Long non-coding RNA ADNCR suppresses adipogenic differentiation by targeting miR-204. Biochem Biophys Acta 1859(7):871–882

    CAS  PubMed  Google Scholar 

  • Li S, Mi L, Yu L, Yu Q, Liu T, Wang GX, Zhao XY, Wu J, Lin JD (2017) Zbtb7b engages the long noncoding RNA Blnc1 to drive brown and beige fat development and thermogenesis. Proc Natl Acad Sci USA 114(34):E7111-e7120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Wu Z, Fu X, Han W (2013) Long Noncoding RNAs: Insights from Biological Features and Functions to Diseases. Med Res Rev 33(3):517–553

    Article  PubMed  CAS  Google Scholar 

  • Lin Y, Wen-Jie Z, Chang-Qing L, Sheng-Xiang A, Yue Z (2020) mir-22-3p/KLF6/MMP14 axis in fibro-adipogenic progenitors regulates fatty infiltration in muscle degeneration. FASEB J 34(9):12691–12701

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Li B, Peng W, Ma Y, Huang Y, Lan X, Lei C, Qi X, Liu GE, Chen H (2019) LncRNA-MEG3 promotes bovine myoblast differentiation by sponging miR-135. J Cell Physiol 234(10):18361–18370

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Chen Q, Wang Y (2020) MiR-125b-5p suppresses the bladder cancer progression via targeting HK2 and suppressing PI3K/AKT pathway. Hum Cell 33(1):185–194

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Sheng L, Miao H, Saunders TL, MacDougald OA, Koenig RJ, Xu B (2014a) SRA gene knockout protects against diet-induced obesity and improves glucose tolerance. J Biol Chem 289(19):13000–13009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Xu R, Gerin I, Cawthorn WP, Macdougald OA, Chen XW, Saltiel AR, Koenig RJ, Xu B (2014) SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating insulin receptor gene expression and downstream signaling. PloS one 9(4):e95416

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matsuzaki S (2011) DNA microarray analysis in endometriosis for development of more effective targeted therapies. Front Biosci (elite Ed) 3:1139–1153

    Article  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  PubMed  Google Scholar 

  • Mi L, Zhao XY, Li S, Yang G, Lin JD (2017) Conserved function of the long noncoding RNA Blnc1 in brown adipocyte differentiation. Mol Metab 6(1):101–110

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seravalle G, Grassi G (2017) Obesity and hypertension. Pharmacol Res 122:1–7

    Article  CAS  PubMed  Google Scholar 

  • Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi C, Huang F, Gu X, Zhang M, Wen J, Wang X, You L, Cui X, Ji C, Guo X (2016) Adipogenic miRNA and meta-signature miRNAs involved in human adipocyte differentiation and obesity. Oncotarget 7(26):40830–40845

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi X, Sun M, Liu H, Yao Y, Song Y (2013) Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett 339(2):159–166

    Article  CAS  PubMed  Google Scholar 

  • Stamatopoulos A, Stamatopoulos T, Gamie Z, Kenanidis E, Ribeiro RDC, Rankin KS, Gerrand C, Dalgarno K, Tsiridis E (2019) Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice. J Bone Onco 16:100231

    Article  Google Scholar 

  • Tang S, Zhu W, Zheng F, Gui W, Zhang W, Lin X, Li H (2020) The long noncoding RNA Blnc1 protects against diet-induced obesity by promoting mitochondrial function in white fat. Diabet Metab Syndr Obes 13:1189–1201

    Article  CAS  Google Scholar 

  • Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vecchié A, Dallegri F, Carbone F, Bonaventura A, Liberale L, Portincasa P, Frühbeck G, Montecucco F (2018) Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med 48:6–17

    Article  PubMed  Google Scholar 

  • Wang F, Yuan JH, Wang SB, Yang F, Yuan SX, Ye C, Yang N, Zhou WP, Li WL, Li W, Sun SH (2014) Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology 60(4):1278–1290

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Liu W, Liu Y, Cui J, Zhao Z, Cao H, Fu Z, Liu B (2018) Long noncoding RNA H19 mediates LCoR to impact the osteogenic and adipogenic differentiation of mBMSCs in mice through sponging miR-188. J Cell Physiol 233(9):7435–7446

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Lachmann A, Ma’ayan A (2019) Mining data and metadata from the gene expression omnibus. Biophys Rev 11(1):103–110

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Wong N, Wang X (2015) miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43:D146-152

    Article  CAS  PubMed  Google Scholar 

  • Xiao T, Liu L, Li H, Sun Y, Luo H, Li T, Wang S, Dalton S, Zhao RC, Chen R (2015) Long noncoding RNA ADINR regulates adipogenesis by transcriptionally activating C/EBPα. Stem Cell Rep 5(5):856–865

    Article  CAS  Google Scholar 

  • Xie C, Mao X, Huang J, Ding Y, Wu J, Dong S, Kong L, Gao G, Li CY, Wei L (2011) KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res 39:W316-322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu B, Gerin I, Miao H, Vu-Phan D, Johnson CN, Xu R, Chen XW, Cawthorn WP, MacDougald OA, Koenig RJ (2010) Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity. PloS One 5(12):e14199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y, Du H, Wei S, Feng L, Li J, Yao F, Zhang M, Hatch GM, Chen L (2018) Adipocyte-derived exosomal MiR-27a induces insulin resistance in skeletal muscle through repression of PPARγ. Theranostics 8(8):2171–2188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang CJ, Liu C, Wang YX, Zhu N, Hu ZY, Liao DF, Qin L (2019) Long non-coding RNA-SRA promotes neointimal hyperplasia and vascular smooth muscle cells proliferation via MEK-ERK-CREB pathway. Vascul Pharmacol 116:16–23

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science (new York, NY) 322(5902):750–756

    Article  CAS  Google Scholar 

  • Zheng Y, Cai B, Li X, Li D, Yin G (2019) MiR-125b-5p and miR-181b-5p inhibit keratinocyte proliferation in skin by targeting Akt3. Eur J Pharmacol 862:172659

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

All the authors acknowledge and thank their respective institutes & universities.

Funding

This work was supported by grants from the National Key Research and Development Program of China (2018YFD0501700), the National Key Technology Support Program (2015BAD03B04), the National Beef and Yak Industrial Technology System (CARS-37), the Agricultural Science and Technology Innovation and Transformation Project of Shaanxi Province (NYKJ-2018-LY09) and the Technical Innovation Engineering Project of Shaanxi Province (2016 KTCL02-15).

Author information

Author notes

  1. Chengcheng Liang and Sayed Haidar Abbas Raza have contributed equally to this work.

Authors and Affiliations

  1. College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, People’s Republic of China

    Chengcheng Liang, Sayed Haidar Abbas Raza, Yanrong Feng & Linsen Zan

  2. Faculty of Health & Medical Science, Hamdard University, Karachi, 75270, Pakistan

    Muhammad Abuzar Raza Naqvi

  3. Department of Livestock Management, Breeding and Genetics, The University of Agriculture Peshawar, Peshawar, Pakistan

    Rajwali Khan

  4. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, 71491, Kingdom of Saudi Arabia

    Zuhair M. Mohammedsaleh

  5. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Kingdom of Saudi Arabia

    Abdullah F. Shater

  6. Biology department, Faculty of Science, Taibah University, Medina, Kingdom of Saudi Arabia

    Bassam M. Al-ahmadi

  7. Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Kingdom of Saudi Arabia

    Fayez M. Saleh

  8. Department of Dermatology, Hospital, Xian Jiaotong University, 157 Xiwu Road, Xi’an, 710004, Shaanxi Province, China

    Muhammad Ahsan Bilal

  9. National Beef Cattle Improvement Center, Northwest A&F University, Yangling, 712100, Shaanxi, China

    Linsen Zan

Authors
  1. Chengcheng Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sayed Haidar Abbas Raza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhammad Abuzar Raza Naqvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanrong Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rajwali Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zuhair M. Mohammedsaleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Abdullah F. Shater
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bassam M. Al-ahmadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fayez M. Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Muhammad Ahsan Bilal
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Linsen Zan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CL and SHAR conceptualization, data curation, formal analysis, investigation, methodology, software, validation, writing—original draft, writing—review and editing. MARN and RK; YF conceptualization, data curation, formal analysis, methodology, software, validation, writing—review and editing. ZMM and AFS, Data curation, formal analysis, writing—review and editing. BMA and FMS Writing—review and editing. MAB software, methodology, visualization software. LZ: conceptualization, funding acquisition, project administration, resources, supervision, visualization, writing—review and editing.

Corresponding author

Correspondence to Linsen Zan.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical Approval

The data used in this study met the following criteria: these relevant data were obtained on basis of the GEO ethics committee, which is open access and public; therefore, there is no need to worry about approval.

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

Liang, C., Raza, S.H.A., Naqvi, M.A.R. et al. Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells. Biochem Genet 60, 543–557 (2022). https://doi.org/10.1007/s10528-021-10115-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-021-10115-1

Keywords

Search

Navigation