Skip to content
2000
image of Exploring the Role of Long Non-Coding RNAs in Mediating Cisplatin Resistance in Colorectal Cancer

Abstract

Colorectal cancer (CRC) usually begins as adenomatous polyps in the colorectal or rectal epithelial cells. Currently, there are no reliable biomarkers for early CRC screening or prognostic prediction, leading to late-stage diagnoses when surgical options may no longer be viable. The disease is driven by mutations in oncogenes, tumor suppressor genes, and DNA repair genes, with rapid growth and metastasis contributing to treatment failure. Over the past two decades, research on non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs), has expanded significantly, revealing their critical roles in cancer biology. LncRNAs are involved in numerous biological processes such as cell proliferation, apoptosis, metabolism, and drug resistance, and they are often abnormally expressed in various cancers, including hepatocellular carcinoma, pancreatic cancer, and bladder cancer. In CRC, lncRNAs play a regulatory role by influencing cell cycle, proliferation, apoptosis, and epithelial-mesenchymal transition, and some have been shown to affect CRC cell proliferation, invasion, and resistance to cisplatin, highlighting their potential as therapeutic targets and biomarkers in cancer treatment. This review highlights current investigations on the functions and mechanisms of lncRNAs in cisplatin resistance in CRC. Such overview is anticipated to contribute to figuring out that lncRNAs can be applied as a promising target gene to develop drug resistance and remedial efficacy.

Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096376480250408070103
2025-05-12
2025-09-13
Loading full text...

Full text loading...

References

  1. Azizidoost S. Nasrolahi A. Ghaedrahmati F. Kempisty B. Mozdziak P. Radoszkiewicz K. Farzaneh M. The pathogenic roles of lncRNA-Taurine upregulated 1 (TUG1) in colorectal cancer. Cancer Cell Int. 2022 22 1 335 10.1186/s12935‑022‑02745‑1 36333703
    [Google Scholar]
  2. White M.T. Sears C.L. The microbial landscape of colorectal cancer. Nat. Rev. Microbiol. 2024 22 4 240 254 10.1038/s41579‑023‑00973‑4 37794172
    [Google Scholar]
  3. Cherkasova V. Ilnytskyy Y. Kovalchuk O. Kovalchuk I. Targeting colorectal cancer: Unravelling the transcriptomic impact of cisplatin and high-THC cannabis extract. Int. J. Mol. Sci. 2024 25 8 4439 10.3390/ijms25084439 38674023
    [Google Scholar]
  4. Mármol I. Sánchez-de-Diego C. Pradilla Dieste A. Cerrada E. Rodriguez Yoldi M. Colorectal carcinoma: A general overview and future perspectives in colorectal cancer. Int. J. Mol. Sci. 2017 18 1 197 10.3390/ijms18010197 28106826
    [Google Scholar]
  5. Maida M. Dahiya D.S. Shah Y.R. Tiwari A. Gopakumar H. Vohra I. Khan A. Jaber F. Ramai D. Facciorusso A. Screening and surveillance of colorectal cancer: A review of the literature. Cancers 2024 16 15 2746 10.3390/cancers16152746 39123473
    [Google Scholar]
  6. Nguyen H. Duong H.Q. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy (Review). Oncol. Lett. 2018 16 1 9 18 10.3892/ol.2018.8679 29928381
    [Google Scholar]
  7. Benitez-Majano S. Fowler H. Maringe C. Di Girolamo C. Rachet B. Deriving stage at diagnosis from multiple population-based sources: Colorectal and lung cancer in England. Br. J. Cancer 2016 115 3 391 400 10.1038/bjc.2016.177 27328310
    [Google Scholar]
  8. Ping G. Xiong W. Zhang L. Li Y. Zhang Y. Zhao Y. Silencing long noncoding RNA PVT1 inhibits tumorigenesis and cisplatin resistance of colorectal cancer. Am. J. Transl. Res. 2018 10 1 138 149 29423000
    [Google Scholar]
  9. Pan J.J. Xie X.J. Li X. Chen W. Long non-coding RNAs and drug resistance. Asian Pac. J. Cancer Prev. 2016 16 18 8067 8073 10.7314/APJCP.2015.16.18.8067 26745040
    [Google Scholar]
  10. Gherman A. Balacescu L. Gheorghe-Cetean S. Vlad C. Balacescu O. Irimie A. Lisencu C. Current and new predictors for treatment response in metastatic colorectal cancer. The role of circulating miRNAs as biomarkers. Int. J. Mol. Sci. 2020 21 6 2089 10.3390/ijms21062089 32197436
    [Google Scholar]
  11. Jiang W. Yan Y. Chen M. Luo G. Hao J. Pan J. Hu S. Guo P. Li W. Wang R. Zuo Y. Sun Y. Sui S. Yu W. Pan Z. Zou K. Zheng Z. Deng W. Wu X. Guo W. Aspirin enhances the sensitivity of colon cancer cells to cisplatin by abrogating the binding of NF-κB to the COX-2 promoter. Aging 2020 12 1 611 627 10.18632/aging.102644 31905343
    [Google Scholar]
  12. Micallef I. Baron B. The mechanistic roles of ncRNAs in promoting and supporting chemoresistance of colorectal cancer. Noncoding RNA 2021 7 2 24 10.3390/ncrna7020024 33807355
    [Google Scholar]
  13. Di Martino M.T. Riillo C. Scionti F. Grillone K. Polerà N. Caracciolo D. Arbitrio M. Tagliaferri P. Tassone P. miRNAs and lncRNAs as novel therapeutic targets to improve cancer immunotherapy. Cancers 2021 13 7 1587 10.3390/cancers13071587 33808190
    [Google Scholar]
  14. Fu D. Lu C. Qu X. Li P. Chen K. Shan L. Zhu X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis. Aging 2019 11 19 8374 8385 10.18632/aging.102325 31600142
    [Google Scholar]
  15. Wei L. Wang X. Lv L. Liu J. Xing H. Song Y. Xie M. Lei T. Zhang N. Yang M. The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma. Mol. Cancer 2019 18 1 147 10.1186/s12943‑019‑1086‑z 31651347
    [Google Scholar]
  16. Xiong G. Liu C. Yang G. Feng M. Xu J. Zhao F. You L. Zhou L. Zheng L. Hu Y. Wang X. Zhang T. Zhao Y. Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer. J. Hematol. Oncol. 2019 12 1 97 10.1186/s13045‑019‑0777‑7 31514732
    [Google Scholar]
  17. Martens-Uzunova E.S. Böttcher R. Croce C.M. Jenster G. Visakorpi T. Calin G.A. Long noncoding RNA in prostate, bladder, and kidney cancer. Eur. Urol. 2014 65 6 1140 1151 10.1016/j.eururo.2013.12.003 24373479
    [Google Scholar]
  18. Kaller M. Götz U. Hermeking H. Loss of p53-inducible long non-coding RNA LINC01021 increases chemosensitivity. Oncotarget 2017 8 61 102783 102800 10.18632/oncotarget.22245 29262524
    [Google Scholar]
  19. Zhao C. Jiang Q. Chen L. Chen W. LncRNA LINC01535 promotes colorectal cancer development and chemoresistance by sponging miR‑761. Exp. Ther. Med. 2021 22 1 685 10.3892/etm.2021.10117 33986850
    [Google Scholar]
  20. Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg. Chem. 2019 88 102925 10.1016/j.bioorg.2019.102925 31003078
    [Google Scholar]
  21. Zoń A. Bednarek I. Cisplatin in ovarian cancer treatment—known limitations in therapy force new solutions. Int. J. Mol. Sci. 2023 24 8 7585 10.3390/ijms24087585 37108749
    [Google Scholar]
  22. Baik M.H. Friesner R.A. Lippard S.J. Theoretical study of cisplatin binding to purine bases: Why does cisplatin prefer guanine over adenine? J. Am. Chem. Soc. 2003 125 46 14082 14092 10.1021/ja036960d 14611245
    [Google Scholar]
  23. Rocha C.R.R. Silva M.M. Quinet A. Cabral-Neto J.B. Menck C.F.M. DNA repair pathways and cisplatin resistance: An intimate relationship. Clinics 2018 73 Suppl. 1 e478s 10.6061/clinics/2018/e478s 30208165
    [Google Scholar]
  24. Chandra A. Pius C. Nabeel M. Nair M. Vishwanatha J.K. Ahmad S. Basha R. Ovarian cancer: Current status and strategies for improving therapeutic outcomes. Cancer Med. 2019 8 16 7018 7031 10.1002/cam4.2560 31560828
    [Google Scholar]
  25. Borkar P. Bhandari P. Yadav S. Prabhu A. Cisplatin resistance in ovarian cancer: Classical outlook and newer perspectives. Biomed. Pharmacol. J. 2021 14 4 1993 2005 10.13005/bpj/2297
    [Google Scholar]
  26. Brozovic A. Ambriović-Ristov A. Osmak M. The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin. Crit. Rev. Toxicol. 2010 40 4 347 359 10.3109/10408441003601836 20163198
    [Google Scholar]
  27. Xu J. Gewirtz D.A. Is autophagy always a barrier to cisplatin therapy? Biomolecules 2022 12 3 463 10.3390/biom12030463 35327655
    [Google Scholar]
  28. Siddik Z.H. Cisplatin: Mode of cytotoxic action and molecular basis of resistance. Oncogene 2003 22 47 7265 7279 10.1038/sj.onc.1206933 14576837
    [Google Scholar]
  29. Skowron M.A. Melnikova M. Van Roermund J.G.H. Romano A. Albers P. Thomale J. Schulz W.A. Niegisch G. Hoffmann M.J. Multifaceted mechanisms of cisplatin resistance in long-term treated urothelial carcinoma cell lines. Int. J. Mol. Sci. 2018 19 2 590 10.3390/ijms19020590 29462944
    [Google Scholar]
  30. Manohar S. Leung N. Cisplatin nephrotoxicity: A review of the literature. J. Nephrol. 2018 31 1 15 25 10.1007/s40620‑017‑0392‑z 28382507
    [Google Scholar]
  31. Ji D. Wang Y. Li H. Sun B. Luo X. Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression. Biochem. Biophys. Res. Commun. 2019 512 2 176 181 10.1016/j.bbrc.2019.03.049 30879766
    [Google Scholar]
  32. Dong L. Qian J. Chen F. Fan Y. Long J. LINC00461 promotes cell migration and invasion in breast cancer through miR‐30a‐5p/integrin β3 axis. J. Cell. Biochem. 2019 120 4 4851 4862 10.1002/jcb.27435 30623482
    [Google Scholar]
  33. Qu W. Huang W. Yang F. Ju H. Zhu G. Long noncoding RNA LINC00461 mediates cisplatin resistance of rectal cancer via miR-593-5p/CCND1 axis. Biomed. Pharmacother. 2020 124 109740 10.1016/j.biopha.2019.109740 31972361
    [Google Scholar]
  34. Yan L. Zhang Y. Li K. Wang M. Li J. Qi Z. Wu J. Wang Z. Ling L. Liu H. Wu Y. Lu X. Xu L. Zhu Y. Zhang Y. miR-593-5p inhibit cell proliferation by targeting PLK1 in non small cell lung cancer cells. Pathol. Res. Pract. 2020 216 2 152786 10.1016/j.prp.2019.152786 31864714
    [Google Scholar]
  35. Zhan K. Pan H. Zhou Z. Tang W. Ye Z. Huang S. Luo L. Biological role of long non-coding RNA KCNQ1OT1 in cancer progression. Biomed. Pharmacother. 2023 169 115876 10.1016/j.biopha.2023.115876 37976888
    [Google Scholar]
  36. Zheng Z. You H. Feng Y. Zhang Z. LncRNA KCNQ1OT1 is a key factor in the reversal effect of curcumin on cisplatin resistance in the colorectal cancer cells. Mol. Cell. Biochem. 2021 476 7 2575 2585 10.1007/s11010‑020‑03856‑x 32757174
    [Google Scholar]
  37. Cui Z. Han B. Wang X. Li Z. Wang J. Lv Y. Long non-coding RNA TTN-AS1 promotes the proliferation and invasion of colorectal cancer cells by activating miR-497-mediated PI3K/Akt/mTOR signaling. OncoTargets Ther. 2019 12 11531 11539 10.2147/OTT.S229104 31920341
    [Google Scholar]
  38. Zendehdel E. Abdollahi E. Momtazi-Borojeni A.A. Korani M. Alavizadeh S.H. Sahebkar A. The molecular mechanisms of curcumin’s inhibitory effects on cancer stem cells. J. Cell. Biochem. 2019 120 4 4739 4747 10.1002/jcb.27757 30269360
    [Google Scholar]
  39. Rezaee R. Momtazi A.A. Monemi A. Sahebkar A. Curcumin: A potentially powerful tool to reverse cisplatin-induced toxicity. Pharmacol. Res. 2017 117 218 227 10.1016/j.phrs.2016.12.037 28042086
    [Google Scholar]
  40. Wu F. Zhu Y. Zhou C. Gui W. Li H. Lin X. Regulation mechanism and pathogenic role of lncRNA plasmacytoma variant translocation 1 (PVT1) in human diseases. Genes Dis. 2023 10 3 901 914 10.1016/j.gendis.2022.05.037 37396533
    [Google Scholar]
  41. Neophytou C.M. Trougakos I.P. Erin N. Papageorgis P. Apoptosis deregulation and the development of cancer multi-drug resistance. Cancers 2021 13 17 4363 10.3390/cancers13174363 34503172
    [Google Scholar]
  42. Lin G.L. Ting H.J. Tseng T.C. Juang V. Lo Y.L. Modulation of the mRNA-binding protein HuR as a novel reversal mechanism of epirubicin-triggered multidrug resistance in colorectal cancer cells. PLoS One 2017 12 10 e0185625 10.1371/journal.pone.0185625 28968471
    [Google Scholar]
  43. Takahashi Y. Sawada G. Kurashige J. Uchi R. Matsumura T. Ueo H. Takano Y. Eguchi H. Sudo T. Sugimachi K. Yamamoto H. Doki Y. Mori M. Mimori K. Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers. Br. J. Cancer 2014 110 1 164 171 10.1038/bjc.2013.698 24196785
    [Google Scholar]
  44. Guo H. Zhao L. Shi B. Bao J. Zheng D. Zhou B. Shi J. GALNT5 uaRNA promotes gastric cancer progression through its interaction with HSP90. Oncogene 2018 37 33 4505 4517 10.1038/s41388‑018‑0266‑4 29743591
    [Google Scholar]
  45. Zhong Z. Bai R. Xu J. LncRNA GALNT5 uaRNA promotes cisplatin resistance in colorectal cancer via NF-κB/MDR1/MRP1/pathway. Research Square 2022 10.21203/rs.3.rs‑1624750/v1
    [Google Scholar]
  46. Kadkol H. Jain V. Patil A. Multi drug resistance in cancer therapy-an overview. J. Crit. Rev. 2019 6 6 1 6 10.22159/jcr.2019v6i6.35673
    [Google Scholar]
  47. Wang Y. Xue K. Guan Y. Jin Y. Liu S. Wang Y. Liu S. Wang L. Han L. Long noncoding RNA LINC00261 suppresses cell proliferation and invasion and promotes cell apoptosis in human choriocarcinoma. Oncol. Res. 2017 25 5 733 742 10.3727/096504016X14772362173376 27983929
    [Google Scholar]
  48. Wang Z.K. Yang L. Wu L.L. Mao H. Zhou Y.H. Zhang P.F. Dai G.H. Long non-coding RNA LINC00261 sensitizes human colon cancer cells to cisplatin therapy. Braz. J. Med. Biol. Res. 2018 51 2 e6793 10.1590/1414‑431x20176793 29267503
    [Google Scholar]
  49. Rahmani F. Tadayyon Tabrizi A. Hashemian P. Alijannejad S. Rahdar H.A. Ferns G.A. Hassanian S.M. Shahidsales S. Avan A. Role of regulatory miRNAs of the Wnt/ β-catenin signaling pathway in tumorigenesis of breast cancer. Gene 2020 754 144892 10.1016/j.gene.2020.144892 32534060
    [Google Scholar]
  50. Yan D. Liu W. Liu Y. Luo M. LINC00261 suppresses human colon cancer progression via sponging miR‐324‐3p and inactivating the Wnt/β‐catenin pathway. J. Cell. Physiol. 2019 234 12 22648 22656 10.1002/jcp.28831 31183860
    [Google Scholar]
  51. Wang Y. Lu Z. Wang N. Feng J. Zhang J. Luan L. Zhao W. Zeng X. Long noncoding RNA DANCR promotes colorectal cancer proliferation and metastasis via miR-577 sponging. Exp. Mol. Med. 2018 50 5 1 17 10.1038/s12276‑018‑0082‑5 29717105
    [Google Scholar]
  52. Yuan S. Wang J. Yang F. Tao Q. Zhang J. Wang L. Yang Y. Liu H. Wang Z. Xu Q. Fan J. Liu L. Sun S. Zhou W. Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma by derepression of CTNNB1. Hepatology 2016 63 2 499 511 10.1002/hep.27893 25964079
    [Google Scholar]
  53. Shi H. Li K. Feng J. Liu G. Feng Y. Zhang X. LncRNA-DANCR interferes with miR-125b-5p/HK2 axis to desensitize colon cancer cells to cisplatin vis activating anaerobic glycolysis. Front. Oncol. 2020 10 1034 10.3389/fonc.2020.01034 32766131
    [Google Scholar]
  54. Peng B. Theng P.Y. Le M.T.N. Essential functions of miR‐125b in cancer. Cell Prolif. 2021 54 2 e12913 10.1111/cpr.12913 33332677
    [Google Scholar]
  55. Xia C. Li Q. Cheng X. Wu T. Gao P. Gu Y. Insulin-like growth factor 2 mRNA-binding protein 2-stabilized long non-coding RNA Taurine up-regulated gene 1 (TUG1) promotes cisplatin-resistance of colorectal cancer via modulating autophagy. Bioengineered 2022 13 2 2450 2469 10.1080/21655979.2021.2012918 35014946
    [Google Scholar]
  56. Huang X. Zhang H. Guo X. Zhu Z. Cai H. Kong X. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer. J. Hematol. Oncol. 2018 11 1 88 10.1186/s13045‑018‑0628‑y 29954406
    [Google Scholar]
  57. Fakhraldeen S.A. Clark R.J. Roopra A. Chin E.N. Huang W. Castorino J. Wisinski K.B. Kim T. Spiegelman V.S. Alexander C.M. Two isoforms of the RNA binding protein, coding region determinant-binding protein (CRD-BP/IGF2BP1), are expressed in breast epithelium and support clonogenic growth of breast tumor cells. J. Biol. Chem. 2015 290 21 13386 13400 10.1074/jbc.M115.655175 25861986
    [Google Scholar]
  58. Zhi S. Li J. Kong X. Xie X. Zhang Q. Fang G. Insulin-like growth factor 2 mRNA binding protein 2 regulates proliferation, migration, and angiogenesis of keratinocytes by modulating heparanase stability. Bioengineered 2021 12 2 11267 11276 10.1080/21655979.2021.2002495 34753397
    [Google Scholar]
  59. Xu Q. Xu J.L. Chen W.Q. Xu W.X. Song Y.X. Tang W.J. Xu D. Jiang M.P. Tang J. Roles and mechanisms of miR-195–5p in human solid cancers. Biomed. Pharmacother. 2022 150 112885 10.1016/j.biopha.2022.112885 35453003
    [Google Scholar]
  60. Bao C. Wang J. Ma W. Wang X. Cheng Y. HDGF: A novel jack-of-all-trades in cancer. Future Oncol. 2014 10 16 2675 2685 10.2217/fon.14.194 25236340
    [Google Scholar]
  61. Nyamao R.M. Wu J. Yu L. Xiao X. Zhang F.M. Roles of DDX5 in the tumorigenesis, proliferation, differentiation, metastasis and pathway regulation of human malignancies. Biochim. Biophys. Acta Rev. Cancer 2019 1871 1 85 98 10.1016/j.bbcan.2018.11.003 30419318
    [Google Scholar]
/content/journals/ccdt/10.2174/0115680096376480250408070103
Loading

  • Article Type:
    Review Article
Keywords: LncRNAs ; cisplatin ; metastasis ; biomarkers ; colorectal cancer ; miRNA
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test