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Long non-coding RNA-based glycolysis-targeted cancer therapy: feasibility, progression and limitations

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Abstract

Metabolism reprogramming is one of the hallmarks of cancer cells, especially glucose metabolism, to promote their proliferation, metastasis and drug resistance. Cancer cells tend to depend on glycolysis for glucose utilization rather than oxidative phosphorylation, which is called the Warburg effect. Genome instability of oncogenes and tumor-inhibiting factors is the culprits for this anomalous glycolytic fueling, which results in dysregulating metabolism-related enzymes and metabolic signaling pathways. It has been extensively demonstrated that protein-coding genes are involved in this process; therefore, glycolysis-targeted therapy has been widely used in anti-tumor combined therapy via small molecular inhibitors of key enzymes and regulatory molecular. The long non-coding RNA, which is a large class of regulatory RNA with longer than 200 nucleotides, is the novel and significant regulator of various biological processes, including metabolic reprogramming. RNA interference and synthetic antisense oligonucleotide for RNA reduction have developed rapidly these years, which presents potent anti-tumor effects both in vitro and in vivo. However, lncRNA-based glycolysis-targeted cancer therapy, as the highly specific and less toxic approach, is still under the preclinical phase. In this review, we highlight the role of lncRNA in glucose metabolism and dissect the feasibility and limitations of this clinical development, which may provide potential targets for cancer therapy.

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Data availability

The data of clinical trials was from https://clinicaltrials.gov/.

Abbreviations

AGPG:

Actin gamma 1 pseudogene

AML:

Acute myeloid leukemia

AMPK:

AMP-activated protein kinase

ANXA2P2:

Annexin A2 Pseudogene 2

ASO:

Antisense oligonucleotide

CHC:

α-Cyano-4-hydroxycinnamic acid

CRC:

Colorectal cancer

ceRNA:

Competing endogenous RNA

CR:

Complete remission

DANCE:

Differentiation antagonizing non-coding RNA

DNMT1:

DNA methyltransferase 1

E2F1:

E2F transcription factor 1

ELF3-AS1:

E74 like ETS transcription factor 3 antisense 1

EGF:

Epidermal growth factor

EC:

Esophageal cancer

EV:

Extracellular vesicle

FCS:

Familial chylomicronemia syndrome

FGFR1:

Fibroblast growth factor receptor type1

FDA:

Food and Drug Administration

FILNC1:

FoxO-induced long non-coding RNA 1

F-1,6-BP:

Fructose-1,6-biphosphate

FBPase:

Fructose-2,6-biphosphatase

F-6-P:

Fructose-6-phosphate

GBS:

Gallbladder cancer

GLUTs:

Glucose transports

G-6-P:

Glucose-6-phosphate

GSH/GSSH:

Glutathione/oxidized glutathione

GADPH:

Glyceraldehyde-3-phosphate dehydrogenase

GLCC1:

Glycolysis-associated lncRNA of colorectal cancer

GPNMB:

Glycoprotein NMB

HCC:

Hepatocellular carcinoma

hnRNP A1:

Heterogeneous nuclear ribonucleoprotein A1

HK:

Hexokinase

HDAC2:

Histone deacetylase

HER:

Hypoxia reaction elements

HIF-1α:

Hypoxia-inducible factor 1α

IGF2BP2:

Insulin-like growth factor 2 mRNA-binding protein 2

IDH:

Isocitrate dehydrogenase

LDH:

Lactate dehydrogenase

LNA:

Locked nuclear acid

LncRNA:

Long non-coding RNA

mTOR:

Mammalian target of rapamycin

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

MCT:

Monocarboxylate transport family

MM:

Multiple myeloma

NBR2:

Neighbor of BRCA1 gene 2

NcRNAs:

Non-coding RNAs

NSCLC:

Non-small cell lung cancer

OSCC:

Oral squamous cell carcinoma

OXPHOS:

Oxidative phosphorylation

TIGAR:

P53-induced glycolysis and apoptosis regulator

PFK-1:

6-Phosphofructokinase-1

PFK-2/PFKFB:

6-Phosphofructokinase-2/fructose-2,6-biphosphatase

PPP:

Pentose phosphate pathway

PI3K:

Phosphatidylinositol-3-hydroxykinase

PEP:

Phosphoenolpyruvate

PVT1:

Plasmacytoma variant translocation

PET:

Positron emission tomography scans

PHD:

Proline hydroxylase domain

PDH:

Pyruvate dehydrogenase

PDK:

Pyruvate dehydrogenase kinase

PK:

Pyruvate kinase

PPARA:

Peroxisome proliferator-activated receptor alpha

ROS:

Reactive oxygen species

RCC:

Renal cell carcinoma

RNAi:

RNA interference

RRM2:

M2 subunit of ribonucleotide reductase

SIRT1:

Deacetylases Sirtuin

siRNA:

Small interference RNA

SGLT:

Sodium-dependent glucose transporter family

SCO2:

Synthesis of cytochrome c oxidase 2

SOX:

Cytochrome c oxidase complex

TF:

Transcriptional factors

TCA:

Tricarboxylic acid

TNBC:

Triple-negative breast cancer

TSC1 and TSC2:

Tuberous sclerosis 1,2

ME:

Tumor microenvironment

TAM:

Tumor-associated macrophages

VHL:

Von Hipple-Lindau protein

XIST:

X-inactive specific transcript

18F-FDG:

18F-labeled 2-fluoro-2-deoxy-d-glucose

2-DG:

2-Deoxyglucose

3-BrPA:

3-Bromopyruvate

α-DG:

α-Hydroxyglutarate

α-KG:

α-Ketoglutarate

References

  1. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics. CA 69(1):7–34. https://doi.org/10.3322/caac.21551

    Article  PubMed  Google Scholar 

  2. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. https://doi.org/10.1016/s0092-8674(00)81683-9

    Article  CAS  PubMed  Google Scholar 

  3. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  4. Pavlova NN, Thompson CB (2016) The emerging hallmarks of cancer metabolism. Cell Metab 23(1):27–47. https://doi.org/10.1016/j.cmet.2015.12.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Warburg O (1956) On the origin of cancer cells. Science (New York, NY) 123(3191):309–314. https://doi.org/10.1126/science.123.3191.309

    Article  CAS  Google Scholar 

  6. Warburg O (1928) The chemical constitution of respiration ferment. Science (New York, NY) 68(1767):437–443. https://doi.org/10.1126/science.68.1767.437

    Article  CAS  Google Scholar 

  7. Warburg O (1956) On respiratory impairment in cancer cells. Science (New York, NY) 124(3215):269–270

    CAS  Google Scholar 

  8. Wang T, Marquardt C, Foker J (1976) Aerobic glycolysis during lymphocyte proliferation. Nature 261(5562):702–705. https://doi.org/10.1038/261702a0

    Article  CAS  PubMed  Google Scholar 

  9. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, NY) 324(5930):1029–1033. https://doi.org/10.1126/science.1160809

    Article  CAS  Google Scholar 

  10. Peppicelli S, Bianchini F, Calorini L (2014) Extracellular acidity, a “reappreciated” trait of tumor environment driving malignancy: perspectives in diagnosis and therapy. Cancer Metastasis Rev 33(2–3):823–832. https://doi.org/10.1007/s10555-014-9506-4

    Article  CAS  PubMed  Google Scholar 

  11. Shiraishi T, Verdone JE, Huang J, Kahlert UD, Hernandez JR, Torga G, Zarif JC, Epstein T, Gatenby R, McCartney A, Elisseeff JH, Mooney SM, An SS, Pienta KJ (2015) Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells. Oncotarget 6(1):130–143. https://doi.org/10.18632/oncotarget.2766

    Article  PubMed  Google Scholar 

  12. Abdel-Wahab AF, Mahmoud W, Al-Harizy RM (2019) Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol Res 150:104511. https://doi.org/10.1016/j.phrs.2019.104511

    Article  CAS  PubMed  Google Scholar 

  13. Razavi ZS, Tajiknia V, Majidi S, Ghandali M, Mirzaei HR, Rahimian N, Hamblin MR, Mirzaei H (2021) Gynecologic cancers and non-coding RNAs: epigenetic regulators with emerging roles. Crit Rev Oncol Hematol 157:103192. https://doi.org/10.1016/j.critrevonc.2020.103192

    Article  PubMed  Google Scholar 

  14. Beermann J, Piccoli MT, Viereck J, Thum T (2016) Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96(4):1297–1325. https://doi.org/10.1152/physrev.00041.2015

    Article  CAS  PubMed  Google Scholar 

  15. Vafadar A, Shabaninejad Z, Movahedpour A, Mohammadi S, Fathullahzadeh S, Mirzaei HR, Namdar A, Savardashtaki A, Mirzaei H (2019) Long non-coding RNAs as epigenetic regulators in cancer. Curr Pharm Des 25(33):3563–3577. https://doi.org/10.2174/1381612825666190830161528

    Article  CAS  PubMed  Google Scholar 

  16. Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482(7385):339–346. https://doi.org/10.1038/nature10887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mirzaei H, Hamblin MR (2020) Regulation of glycolysis by non-coding RNAs in cancer: switching on the Warburg effect. Molecular therapy oncolytics 19:218–239. https://doi.org/10.1016/j.omto.2020.10.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun H, Huang Z, Sheng W, Xu MD (2018) Emerging roles of long non-coding RNAs in tumor metabolism. J Hematol Oncol 11(1):106. https://doi.org/10.1186/s13045-018-0648-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vincent EE, Coelho PP, Blagih J, Griss T, Viollet B, Jones RG (2015) Differential effects of AMPK agonists on cell growth and metabolism. Oncogene 34(28):3627–3639. https://doi.org/10.1038/onc.2014.301

    Article  CAS  PubMed  Google Scholar 

  20. Szablewski L (2013) Expression of glucose transporters in cancers. Biochim Biophys Acta 1835(2):164–169. https://doi.org/10.1016/j.bbcan.2012.12.004

    Article  CAS  PubMed  Google Scholar 

  21. Yu M, Yongzhi H, Chen S, Luo X, Lin Y, Zhou Y, Jin H, Hou B, Deng Y, Tu L, Jian Z (2017) The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis. Oncotarget 8(26):43356–43367. https://doi.org/10.18632/oncotarget.17445

    Article  PubMed  PubMed Central  Google Scholar 

  22. Phadngam S, Castiglioni A, Ferraresi A, Morani F, Follo C, Isidoro C (2016) PTEN dephosphorylates AKT to prevent the expression of GLUT1 on plasmamembrane and to limit glucose consumption in cancer cells. Oncotarget 7(51):84999–85020. https://doi.org/10.18632/oncotarget.13113

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chu H, Li Z, Gan Z, Yang Z, Wu Z, Rong M (2019) LncRNA ELF3-AS1 is involved in the regulation of oral squamous cell carcinoma cell proliferation by reprogramming glucose metabolism. Onco Targets Ther 12:6857–6863. https://doi.org/10.2147/ott.S217473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wei S, Fan Q, Yang L, Zhang X, Ma Y, Zong Z, Hua X, Su D, Sun H, Li H, Liu Z (2017) Promotion of glycolysis by HOTAIR through GLUT1 upregulation via mTOR signaling. Oncol Rep 38(3):1902–1908. https://doi.org/10.3892/or.2017.5840

    Article  CAS  PubMed  Google Scholar 

  25. Patra KC, Hay N (2013) Hexokinase 2 as oncotarget. Oncotarget 4(11):1862–1863. https://doi.org/10.18632/oncotarget.1563

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chen J, Yu Y, Li H, Hu Q, Chen X, He Y, Xue C, Ren F, Ren Z, Li J, Liu L, Duan Z, Cui G, Sun R (2019) Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer. Mol Cancer 18(1):33. https://doi.org/10.1186/s12943-019-0947-9

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shi H, Li K, Feng J, Liu G, Feng Y, Zhang X (2020) LncRNA-DANCR interferes with miR-125b-5p/HK2 Axis to desensitize colon cancer cells to Cisplatin vis activating anaerobic glycolysis. Front Oncol 10:1034. https://doi.org/10.3389/fonc.2020.01034

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tang D, Yang Z, Long F, Luo L, Yang B, Zhu R, Sang X, Cao G, Wang K (2019) Long noncoding RNA MALAT1 mediates stem cell-like properties in human colorectal cancer cells by regulating miR-20b-5p/Oct4 axis. J Cell Physiol 234(11):20816–20828. https://doi.org/10.1002/jcp.28687

    Article  CAS  PubMed  Google Scholar 

  29. Al Hasawi N, Alkandari MF, Luqmani YA (2014) Phosphofructokinase: a mediator of glycolytic flux in cancer progression. Crit Rev Oncol Hematol 92(3):312–321. https://doi.org/10.1016/j.critrevonc.2014.05.007

    Article  PubMed  Google Scholar 

  30. Yalcin A, Clem BF, Imbert-Fernandez Y, Ozcan SC, Peker S, O’Neal J, Klarer AC, Clem AL, Telang S, Chesney J (2014) 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27. Cell Death Dis 5(7):e1337. https://doi.org/10.1038/cddis.2014.292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu J, Liu ZX, Wu QN, Lu YX, Wong CW, Miao L, Wang Y, Wang Z, Jin Y, He MM, Ren C, Wang DS, Chen DL, Pu HY, Feng L, Li B, Xie D, Zeng MS, Huang P, Lin A, Lin D, Xu RH, Ju HQ (2020) Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming. Nat Commun 11(1):1507. https://doi.org/10.1038/s41467-020-15112-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xing Z, Zhang Y, Liang K, Yan L, Xiang Y, Li C, Hu Q, Jin F, Putluri V, Putluri N, Coarfa C, Sreekumar A, Park PK, Nguyen TK, Wang S, Zhou J, Zhou Y, Marks JR, Hawke DH, Hung MC, Yang L, Han L, Ying H, Lin C (2018) Expression of long noncoding RNA YIYA promotes glycolysis in breast cancer. Cancer Res 78(16):4524–4532. https://doi.org/10.1158/0008-5472.Can-17-0385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Israelsen WJ, Vander Heiden MG (2015) Pyruvate kinase: function, regulation and role in cancer. Semin Cell Dev Biol 43:43–51. https://doi.org/10.1016/j.semcdb.2015.08.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. David CJ, Chen M, Assanah M, Canoll P, Manley JL (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463(7279):364–368. https://doi.org/10.1038/nature08697

    Article  CAS  PubMed  Google Scholar 

  35. Chen M, David CJ, Manley JL (2012) Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. Nat Struct Mol Biol 19(3):346–354. https://doi.org/10.1038/nsmb.2219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Huang JZ, Chen M, Chen D, Gao XC, Zhu S, Huang H, Hu M, Zhu H, Yan GR (2017) A peptide encoded by a putative lncRNA HOXB-AS3 suppresses colon cancer growth. Mol Cell 68(1):171-184.e176. https://doi.org/10.1016/j.molcel.2017.09.015

    Article  CAS  PubMed  Google Scholar 

  37. Luo W, Hu H, Chang R, Zhong J, Knabel M, O’Meally R, Cole RN, Pandey A, Semenza GL (2011) Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145(5):732–744. https://doi.org/10.1016/j.cell.2011.03.054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang C, Li Y, Yan S, Wang H, Shao X, Xiao M, Yang B, Qin G, Kong R, Chen R, Zhang N (2020) Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2. Nat Commun 11(1):3162. https://doi.org/10.1038/s41467-020-16966-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gao X, Wang H, Yang JJ, Liu X, Liu ZR (2012) Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell 45(5):598–609. https://doi.org/10.1016/j.molcel.2012.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bian Z, Zhang J, Li M, Feng Y, Wang X, Zhang J, Yao S, Jin G, Du J, Han W, Yin Y, Huang S, Fei B, Zou J, Huang Z (2018) LncRNA-FEZF1-AS1 promotes tumor proliferation and metastasis in colorectal cancer by regulating PKM2 signaling. Clin Cancer Res 24(19):4808–4819. https://doi.org/10.1158/1078-0432.Ccr-17-2967

    Article  CAS  PubMed  Google Scholar 

  41. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV (2010) Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA 107(5):2037–2042. https://doi.org/10.1073/pnas.0914433107

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zhou Y, Huang Y, Hu K, Zhang Z, Yang J, Wang Z (2020) HIF1A activates the transcription of lncRNA RAET1K to modulate hypoxia-induced glycolysis in hepatocellular carcinoma cells via miR-100-5p. Cell Death Dis 11(3):176. https://doi.org/10.1038/s41419-020-2366-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Du P, Liao Y, Zhao H, Zhang J, Muyiti K, Mu K (2020) ANXA2P2/miR-9/LDHA axis regulates Warburg effect and affects glioblastoma proliferation and apoptosis. Cell Signal 74:109718. https://doi.org/10.1016/j.cellsig.2020.109718

    Article  CAS  PubMed  Google Scholar 

  44. Payen VL, Mina E, Van Hée VF, Porporato PE, Sonveaux P (2020) Monocarboxylate transporters in cancer. Mol Metab 33:48–66. https://doi.org/10.1016/j.molmet.2019.07.006

    Article  CAS  PubMed  Google Scholar 

  45. Logotheti S, Marquardt S, Gupta SK, Richter C, Edelhäuser BAH, Engelmann D, Brenmoehl J, Söhnchen C, Murr N, Alpers M, Singh KP, Wolkenhauer O, Heckl D, Spitschak A, Pützer BM (2020) LncRNA-SLC16A1-AS1 induces metabolic reprogramming during Bladder Cancer progression as target and co-activator of E2F1. Theranostics 10(21):9620–9643. https://doi.org/10.7150/thno.44176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Woolbright BL, Rajendran G, Harris RA, Taylor JA 3rd (2019) Metabolic flexibility in cancer: targeting the pyruvate dehydrogenase kinase: pyruvate dehydrogenase axis. Mol Cancer Ther 18(10):1673–1681. https://doi.org/10.1158/1535-7163.Mct-19-0079

    Article  CAS  PubMed  Google Scholar 

  47. Xu S, Guo J, Zhang W (2019) lncRNA PCAT19 promotes the proliferation of laryngocarcinoma cells via modulation of the miR-182/PDK4 axis. J Cell Biochem 120(8):12810–12821. https://doi.org/10.1002/jcb.28552

    Article  CAS  PubMed  Google Scholar 

  48. Liu Y, He X, Chen Y, Cao D (2020) Long non-coding RNA LINC00504 regulates the Warburg effect in ovarian cancer through inhibition of miR-1244. Mol Cell Biochem 464(1–2):39–50. https://doi.org/10.1007/s11010-019-03647-z

    Article  CAS  PubMed  Google Scholar 

  49. Kim J, DeBerardinis RJ (2019) Mechanisms and implications of metabolic heterogeneity in cancer. Cell Metab 30(3):434–446. https://doi.org/10.1016/j.cmet.2019.08.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Dang L, Yen K, Attar EC (2016) IDH mutations in cancer and progress toward development of targeted therapeutics. Ann Oncol 27(4):599–608. https://doi.org/10.1093/annonc/mdw013

    Article  CAS  PubMed  Google Scholar 

  51. Xiang S, Gu H, Jin L, Thorne RF, Zhang XD, Wu M (2018) LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect. Proc Natl Acad Sci USA 115(7):E1465-e1474. https://doi.org/10.1073/pnas.1711257115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM (1982) Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 79(24):7824–7827. https://doi.org/10.1073/pnas.79.24.7824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Dang CV (2012) MYC on the path to cancer. Cell 149(1):22–35. https://doi.org/10.1016/j.cell.2012.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Stine ZE, Walton ZE, Altman BJ, Hsieh AL, Dang CV (2015) MYC, metabolism, and cancer. Cancer Discov 5(10):1024–1039. https://doi.org/10.1158/2159-8290.Cd-15-0507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hua Q, Jin M, Mi B, Xu F, Li T, Zhao L, Liu J, Huang G (2019) LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis. J Hematol Oncol 12(1):91. https://doi.org/10.1186/s13045-019-0773-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Xiao ZD, Han L, Lee H, Zhuang L, Zhang Y, Baddour J, Nagrath D, Wood CG, Gu J, Wu X, Liang H, Gan B (2017) Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nat Commun 8(1):783. https://doi.org/10.1038/s41467-017-00902-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tang J, Yan T, Bao Y, Shen C, Yu C, Zhu X, Tian X, Guo F, Liang Q, Liu Q, Zhong M, Chen J, Ge Z, Li X, Chen X, Cui Y, Chen Y, Zou W, Chen H, Hong J, Fang JY (2019) LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc. Nat Commun 10(1):3499. https://doi.org/10.1038/s41467-019-11447-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wang Y, Lu JH, Wu QN, Jin Y, Wang DS, Chen YX, Liu J, Luo XJ, Meng Q, Pu HY, Wang YN, Hu PS, Liu ZX, Zeng ZL, Zhao Q, Deng R, Zhu XF, Ju HQ, Xu RH (2019) LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol Cancer 18(1):174. https://doi.org/10.1186/s12943-019-1105-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ma F, Liu X, Zhou S, Li W, Liu C, Chadwick M, Qian C (2019) Long non-coding RNA FGF13-AS1 inhibits glycolysis and stemness properties of breast cancer cells through FGF13-AS1/IGF2BPs/Myc feedback loop. Cancer Lett 450:63–75. https://doi.org/10.1016/j.canlet.2019.02.008

    Article  CAS  PubMed  Google Scholar 

  60. Semenza GL (2011) Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta 1813(7):1263–1268. https://doi.org/10.1016/j.bbamcr.2010.08.006

    Article  CAS  PubMed  Google Scholar 

  61. Semenza GL (2009) Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Semin Cancer Biol 19(1):12–16. https://doi.org/10.1016/j.semcancer.2008.11.009

    Article  CAS  PubMed  Google Scholar 

  62. Kaelin WG Jr, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30(4):393–402. https://doi.org/10.1016/j.molcel.2008.04.009

    Article  CAS  PubMed  Google Scholar 

  63. Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC (2015) Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep 42(4):841–851. https://doi.org/10.1007/s11033-015-3858-x

    Article  CAS  PubMed  Google Scholar 

  64. Yang F, Zhang H, Mei Y, Wu M (2014) Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect. Mol Cell 53(1):88–100. https://doi.org/10.1016/j.molcel.2013.11.004

    Article  CAS  PubMed  Google Scholar 

  65. Lin A, Li C, Xing Z, Hu Q, Liang K, Han L, Wang C, Hawke DH, Wang S, Zhang Y, Wei Y, Ma G, Park PK, Zhou J, Zhou Y, Hu Z, Zhou Y, Marks JR, Liang H, Hung MC, Lin C, Yang L (2016) The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nat Cell Biol 18(2):213–224. https://doi.org/10.1038/ncb3295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chen P, Zuo H, Xiong H, Kolar MJ, Chu Q, Saghatelian A, Siegwart DJ, Wan Y (2017) Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis. Proc Natl Acad Sci USA 114(3):580–585. https://doi.org/10.1073/pnas.1614035114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y, Tu Q, Yin D, Lin D, Wong PP, Huang D, Xing Y, Zhao J, Li M, Liu Q, Su F, Su S, Song E (2019) Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol 21(4):498–510. https://doi.org/10.1038/s41556-019-0299-0

    Article  CAS  PubMed  Google Scholar 

  68. Vousden KH, Ryan KM (2009) p53 and metabolism. Nat Rev Cancer 9(10):691–700. https://doi.org/10.1038/nrc2715

    Article  CAS  PubMed  Google Scholar 

  69. Khan MR, Xiang S, Song Z, Wu M (2017) The p53-inducible long noncoding RNA TRINGS protects cancer cells from necrosis under glucose starvation. Embo J 36(23):3483–3500. https://doi.org/10.15252/embj.201696239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126(1):107–120. https://doi.org/10.1016/j.cell.2006.05.036

    Article  CAS  PubMed  Google Scholar 

  71. Du W, Amarachintha S, Wilson AF, Pang Q (2016) SCO2 Mediates oxidative stress-induced glycolysis to oxidative phosphorylation switch in hematopoietic stem cells. Stem Cells (Dayton, Ohio) 34(4):960–971. https://doi.org/10.1002/stem.2260

    Article  CAS  Google Scholar 

  72. Chen R, Liu Y, Zhuang H, Yang B, Hei K, Xiao M, Hou C, Gao H, Zhang X, Jia C, Li L, Li Y, Zhang N (2017) Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation. Nucleic Acids Res 45(17):9947–9959. https://doi.org/10.1093/nar/gkx600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Liao M, Liao W, Xu N, Li B, Liu F, Zhang S, Wang Y, Wang S, Zhu Y, Chen D, Xie W, Jiang Y, Cao L, Yang BB, Zhang Y (2019) LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2. EBioMedicine 41:200–213. https://doi.org/10.1016/j.ebiom.2019.01.035

    Article  PubMed  PubMed Central  Google Scholar 

  74. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64(11):3892–3899. https://doi.org/10.1158/0008-5472.Can-03-2904

    Article  CAS  PubMed  Google Scholar 

  75. Li W, Huang K, Wen F, Cui G, Guo H, He Z, Zhao S (2019) LINC00184 silencing inhibits glycolysis and restores mitochondrial oxidative phosphorylation in esophageal cancer through demethylation of PTEN. EBioMedicine 44:298–310. https://doi.org/10.1016/j.ebiom.2019.05.055

    Article  PubMed  PubMed Central  Google Scholar 

  76. Zheng YL, Li L, Jia YX, Zhang BZ, Li JC, Zhu YH, Li MQ, He JZ, Zeng TT, Ban XJ, Yuan YF, Li Y, Guan XY (2019) LINC01554-mediated glucose metabolism reprogramming suppresses tumorigenicity in hepatocellular carcinoma via downregulating PKM2 expression and inhibiting Akt/mTOR signaling pathway. Theranostics 9(3):796–810. https://doi.org/10.7150/thno.28992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cheng Z, Luo C, Guo Z (2020) LncRNA-XIST/microRNA-126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma. J Cell Biochem 121(3):2170–2183. https://doi.org/10.1002/jcb.29440

    Article  CAS  PubMed  Google Scholar 

  78. Hardie DG (2015) Molecular pathways: is AMPK a friend or a foe in cancer? Clin Cancer Res 21(17):3836–3840. https://doi.org/10.1158/1078-0432.Ccr-14-3300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu X, Xiao ZD, Han L, Zhang J, Lee SW, Wang W, Lee H, Zhuang L, Chen J, Lin HK, Wang J, Liang H, Gan B (2016) LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat Cell Biol 18(4):431–442. https://doi.org/10.1038/ncb3328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Liu X, Gan B (2016) lncRNA NBR2 modulates cancer cell sensitivity to phenformin through GLUT1. Cell Cycle 15(24):3471–3481. https://doi.org/10.1080/15384101.2016.1249545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sun LY, Li XJ, Sun YM, Huang W, Fang K, Han C, Chen ZH, Luo XQ, Chen YQ, Wang WT (2018) LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1. Mol Cancer 17(1):127. https://doi.org/10.1186/s12943-018-0879-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhao Y, Liu Y, Lin L, Huang Q, He W, Zhang S, Dong S, Wen Z, Rao J, Liao W, Shi M (2018) The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1. Mol Cancer 17(1):69. https://doi.org/10.1186/s12943-018-0820-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bomanji JB, Costa DC, Ell PJ (2001) Clinical role of positron emission tomography in oncology. Lancet Oncol 2(3):157–164. https://doi.org/10.1016/s1470-2045(00)00257-6

    Article  CAS  PubMed  Google Scholar 

  84. Dalva-Aydemir S, Bajpai R, Martinez M, Adekola KU, Kandela I, Wei C, Singhal S, Koblinski JE, Raje NS, Rosen ST, Shanmugam M (2015) Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin. Clin Cancer Res 21(5):1161–1171. https://doi.org/10.1158/1078-0432.Ccr-14-1088

    Article  CAS  PubMed  Google Scholar 

  85. Sheng Y, Jiang Q, Dong X, Liu J, Liu L, Wang H, Wang L, Li H, Yang X, Dong J (2020) 3-Bromopyruvate inhibits the malignant phenotype of malignantly transformed macrophages and dendritic cells induced by glioma stem cells in the glioma microenvironment via miR-449a/MCT1. Biomed Pharmacother 121:109610. https://doi.org/10.1016/j.biopha.2019.109610

    Article  CAS  PubMed  Google Scholar 

  86. Icard P, Shulman S, Farhat D, Steyaert JM, Alifano M, Lincet H (2018) How the Warburg effect supports aggressiveness and drug resistance of cancer cells? Drug Resist Updates 38:1–11. https://doi.org/10.1016/j.drup.2018.03.001

    Article  Google Scholar 

  87. Vasan N, Baselga J, Hyman DM (2019) A view on drug resistance in cancer. Nature 575(7782):299–309. https://doi.org/10.1038/s41586-019-1730-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Noël G, Langouo Fontsa M, Willard-Gallo K (2018) The impact of tumor cell metabolism on T cell-mediated immune responses and immuno-metabolic biomarkers in cancer. Semin Cancer Biol 52(Pt 2):66–74. https://doi.org/10.1016/j.semcancer.2018.03.003

    Article  CAS  PubMed  Google Scholar 

  89. Ramapriyan R, Caetano MS, Barsoumian HB, Mafra ACP, Zambalde EP, Menon H, Tsouko E, Welsh JW, Cortez MA (2019) Altered cancer metabolism in mechanisms of immunotherapy resistance. Pharmacol Ther 195:162–171. https://doi.org/10.1016/j.pharmthera.2018.11.004

    Article  CAS  PubMed  Google Scholar 

  90. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811. https://doi.org/10.1038/35888

    Article  CAS  PubMed  Google Scholar 

  91. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498. https://doi.org/10.1038/35078107

    Article  CAS  PubMed  Google Scholar 

  92. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464(7291):1067–1070. https://doi.org/10.1038/nature08956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Golan T, Khvalevsky EZ, Hubert A, Gabai RM, Hen N, Segal A, Domb A, Harari G, David EB, Raskin S, Goldes Y, Goldin E, Eliakim R, Lahav M, Kopleman Y, Dancour A, Shemi A, Galun E (2015) RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients. Oncotarget 6(27):24560–24570. https://doi.org/10.18632/oncotarget.4183

    Article  PubMed  PubMed Central  Google Scholar 

  94. Xue VW, Wong SCC, Song G, Cho WCS (2020) Promising RNA-based cancer gene therapy using extracellular vesicles for drug delivery. Expert Opin Biol Ther 20(7):767–777. https://doi.org/10.1080/14712598.2020.1738377

    Article  CAS  PubMed  Google Scholar 

  95. Das M, Musetti S, Huang L (2019) RNA Interference-Based Cancer Drugs: The Roadblocks, and the “Delivery” of the Promise. Nucleic acid therapeutics 29(2):61–66. https://doi.org/10.1089/nat.2018.0762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Mainini F, Eccles MR (2020) Lipid and polymer-based nanoparticle siRNA delivery systems for cancer therapy. Molecules (Basel, Switzerland). https://doi.org/10.3390/molecules25112692

    Article  Google Scholar 

  97. Maruyama R, Yokota T (2020) Knocking down long noncoding RNAs using antisense oligonucleotide gapmers. Methods Mol Biol 2176:49–56. https://doi.org/10.1007/978-1-0716-0771-8_3

    Article  PubMed  Google Scholar 

  98. Post N, Yu R, Greenlee S, Gaus H, Hurh E, Matson J, Wang Y (2019) Metabolism and disposition of volanesorsen, a 2’-O-(2 methoxyethyl) antisense oligonucleotide, across species. Drug Metabol Disposit 47(10):1164–1173. https://doi.org/10.1124/dmd.119.087395

    Article  CAS  Google Scholar 

  99. Amodio N, Stamato MA, Juli G, Morelli E, Fulciniti M, Manzoni M, Taiana E, Agnelli L, Cantafio MEG, Romeo E, Raimondi L, Caracciolo D, Zuccalà V, Rossi M, Neri A, Munshi NC, Tagliaferri P, Tassone P (2018) Drugging the lncRNA MALAT1 via LNA gapmeR ASO inhibits gene expression of proteasome subunits and triggers anti-multiple myeloma activity. Leukemia 32(9):1948–1957. https://doi.org/10.1038/s41375-018-0067-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Fathi Dizaji B (2020) Strategies to target long non-coding RNAs in cancer treatment: progress and challenges. Egypt J Med Hum Genet 21:41. https://doi.org/10.1186/s43042-020-00074-4

    Article  Google Scholar 

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  1. The co-first authors: Xiaman Wang, Ying Shen

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  1. Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157, 5th West Road, Xi’an, 710004, Shaanxi, China

    Rui Liu, Xiaman Wang, Ying Shen & Aili He

  2. National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, China

    Aili He

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All authors contributed to the study conception and design. RL performed the literature search and analysis. RL prepared tables and figures, and drafted the manuscript. AH, YS and XW revised the manuscript.

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Liu, R., Wang, X., Shen, Y. et al. Long non-coding RNA-based glycolysis-targeted cancer therapy: feasibility, progression and limitations. Mol Biol Rep 48, 2713–2727 (2021). https://doi.org/10.1007/s11033-021-06247-7

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