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LncRNA as a multifunctional regulator in cancer multi-drug resistance

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Abstract

Background

Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs).

Methods and results

This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease.

Conclusions

LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.

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References

  1. Peng WX, Koirala P, Mo YY (2017) LncRNA-mediated regulation of cell signaling in cancer . Oncogene 36(41):5661–5667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yang G, Lu X, Yuan L (2014) LncRNA: a link between RNA and cancer. Biochim Biophys Acta 1839(11):1097–1109

    Article  CAS  PubMed  Google Scholar 

  3. Huang Y (2018) The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases. J Cell Mol Med 22(12):5768–5775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pandya G et al (2020) The implication of long non-coding RNAs in the diagnosis, pathogenesis and drug resistance of pancreatic ductal adenocarcinoma and their possible therapeutic potential. Biochim Biophys Acta Rev Cancer 1874(2):188423

    Article  CAS  PubMed  Google Scholar 

  5. Raziq K et al (2020) Competitive endogenous network of lncRNA, miRNA, and mRNA in the chemoresistance of gastrointestinal tract adenocarcinomas. Biomed Pharmacother 130:110570

    Article  CAS  PubMed  Google Scholar 

  6. Li XL et al (2020) emopenA small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cellsemclose. Elife. https://doi.org/10.7554/eLife.53734

    Article  PubMed  PubMed Central  Google Scholar 

  7. Emmrich S et al (2014) LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia. Mol Cancer 13:171

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. St Laurent G, Wahlestedt C, Kapranov P (2015) The Landscape of long noncoding RNA classification. Trends Genet 31(5):239–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12(12):861–874

    Article  CAS  PubMed  Google Scholar 

  10. Sanchez Calle A et al (2018) Emerging roles of long non-coding RNA in cancer. Cancer Sci 109(7):2093–2100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chirila DN et al (2013) Multiple malignant tumors. Chirurgia (Bucur) 108(4):498–502

    CAS  Google Scholar 

  12. Hoang NT et al (2018) A review of soft-tissue sarcomas: translation of biological advances into treatment measures. Cancer Manag Res 10:1089–1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vtorushin SV et al (2014) The phenomenon of multi-drug resistance in the treatment of malignant tumors. Exp Oncol 36(3):144–156

    CAS  PubMed  Google Scholar 

  14. Wang JJ, Lei KF, Han F (2018) Tumor microenvironment: recent advances in various cancer treatments. Eur Rev Med Pharmacol Sci 22(12):3855–3864

    PubMed  Google Scholar 

  15. Bedikian AY, Valdivieso M, Bodey GP (1980) Systemic chemotherapy for advanced gastrointestinal cancer. South Med J 73(8):1046–1052

    Article  CAS  PubMed  Google Scholar 

  16. Li T et al (2016) Molecular mechanisms of long noncoding RNAs on gastric cancer. Oncotarget 7(8):8601–8612

    Article  PubMed  PubMed Central  Google Scholar 

  17. Li X et al (2017) Long noncoding RNAs in head and neck cancer. Oncotarget 8(6):10726–10740

    Article  PubMed  Google Scholar 

  18. Lu S et al (2018) The role of the long non-coding RNA HOXA11-AS in promoting proliferation and metastasis of malignant tumors. Cell Biol Int 42(12):1596–1601

    Article  CAS  PubMed  Google Scholar 

  19. Lv Y, Huang S (2019) Role of non-coding RNA in pancreatic cancer. Oncol Lett 18(4):3963–3973

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao M et al (2014) Long non-coding RNAs involved in gynecological cancer. Int J Gynecol Cancer 24(7):1140–1145

    Article  PubMed  Google Scholar 

  21. Xuan W et al (2019) Crosstalk between the lncRNA UCA1 and microRNAs in cancer. FEBS Lett 593(15):1901–1914

    Article  CAS  PubMed  Google Scholar 

  22. Kong X et al (2020) Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer. J Cancer 11(11):3357–3368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hu M et al (2019) lncRNA CCAT1 is a biomarker for the proliferation and drug resistance of esophageal cancer via the miR-143/PLK1/BUBR1 axis. Mol Carcinog 58(12):2207–2217

    Article  CAS  PubMed  Google Scholar 

  24. Yang Q et al (2020) lncRNA SLC7A11-AS1 Promotes Chemoresistance by Blocking SCF(beta-TRCP)-Mediated Degradation of NRF2 in Pancreatic Cancer. Mol Ther Nucleic Acids 19:974–985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. He W et al (2019) MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer. Oncogene 38(23):4637–4654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Du P et al (2019) LncRNA PVT1 Mediates Antiapoptosis and 5-Fluorouracil Resistance via Increasing Bcl2 Expression in Gastric Cancer. J Oncol 2019:9325407

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Loewen G et al (2014) Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol 7:90

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Kolios G, Moodley Y (2013) Introduction to stem cells and regenerative medicine. Respiration 85(1):3–10

    Article  PubMed  Google Scholar 

  29. Du FY et al (2019) Targeting cancer stem cells in drug discovery: Current state and future perspectives. World J Stem Cells 11(7):398–420

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rajagopal T et al (2020) HOTAIR LncRNA: a novel oncogenic propellant in human cancer. Clin Chim Acta 503:1–18

    Article  CAS  PubMed  Google Scholar 

  31. Alfarouk KO et al (2015) Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int 15:71

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Gottesman MM et al (2016) Toward a Better Understanding of the Complexity of Cancer Drug Resistance. Annu Rev Pharmacol Toxicol 56:85–102

    Article  CAS  PubMed  Google Scholar 

  33. Wu Q et al (2014) Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches. Cancer Lett 347(2):159–166

    Article  CAS  PubMed  Google Scholar 

  34. Liu H et al (2019) Drug Resistance-Related Competing Interactions of lncRNA and mRNA across 19 Cancer Types. Mol Ther Nucleic Acids 16:442–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Allen KE, Weiss GJ (2010) Resistance may not be futile: microRNA biomarkers for chemoresistance and potential therapeutics. Mol Cancer Ther 9(12):3126–3136

    Article  CAS  PubMed  Google Scholar 

  36. Correia de Sousa M et al (2019) Deciphering miRNAs’ action through miRNA editing. Int J Mol Sci. https://doi.org/10.3390/ijms20246249

    Article  PubMed  PubMed Central  Google Scholar 

  37. Feng C et al (2019) LncRNA MALAT1 Promotes Lung Cancer Proliferation and Gefitinib Resistance by Acting as a miR-200a Sponge. Arch Bronconeumol 55(12):627–633

    Article  PubMed  Google Scholar 

  38. Wang H et al (2017) LncRNA UCA1 in anti-cancer drug resistance. Oncotarget 8(38):64638–64650

    Article  PubMed  PubMed Central  Google Scholar 

  39. Yan J et al (2016) LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes. Tumour Biol 37:16345–16355

  40. Luo X et al (2019) Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis. Cancer Cell Int 19:323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang P et al (2017) LncRNA MEG3 enhances cisplatin sensitivity in non-small cell lung cancer by regulating miR-21-5p/SOX7 axis. Onco Targets Ther 10:5137–5149

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ge P et al (2019) lncRNA FOXD2-AS1 confers cisplatin resistance of non-small-cell lung cancer via regulation of miR185-5p-SIX1 axis. Onco Targets Ther 12:6105–6117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wang L, Shang X, Feng Q (2019) LncRNA TATDN1 contributes to the cisplatin resistance of non-small cell lung cancer through TATDN1/miR-451/TRIM66 axis. Cancer Biol Ther 20(3):261–271

    Article  CAS  PubMed  Google Scholar 

  44. Zhu L et al (2015) Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis. Pathol Oncol Res 21(4):1259–1264

    Article  CAS  PubMed  Google Scholar 

  45. Zhang Z, Li M, Zhang Z (2020) lncRNA MALAT1 modulates oxaliplatin resistance of gastric cancer via sponging miR-22-3p. Onco Targets Ther 13:1343–1354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Liu HT et al (2015) MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers. Oncotarget 6(35):37458–37470

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wang H et al (2018) HOTAIR enhanced paclitaxel and doxorubicin resistance in gastric cancer cells partly through inhibiting miR-217 expression. J Cell Biochem 119(9):7226–7234

    Article  CAS  PubMed  Google Scholar 

  48. Panda M, Biswal BK (2019) Cell signaling and cancer: a mechanistic insight into drug resistance. Mol Biol Rep 46(5):5645–5659

    Article  CAS  PubMed  Google Scholar 

  49. Austreid E, Lonning PE, Eikesdal HP (2014) The emergence of targeted drugs in breast cancer to prevent resistance to endocrine treatment and chemotherapy. Expert Opin Pharmacother 15(5):681–700

    Article  CAS  PubMed  Google Scholar 

  50. Chen QY, Costa M (2018) PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis. Mol Pharmacol 94(1):784–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Li T, Wang G (2014) Computer-aided targeting of the PI3K/Akt/mTOR pathway: toxicity reduction and therapeutic opportunities. Int J Mol Sci 15(10):18856–18891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li Z et al (2019) Long noncoding RNA UCA1 confers tamoxifen resistance in breast cancer endocrinotherapy through regulation of the EZH2/p21 axis and the PI3K/AKT signaling pathway. Int J Oncol 54(3):1033–1042

    CAS  PubMed  Google Scholar 

  53. Dai Q et al (2020) LncRNA UCA1 promotes cisplatin resistance in gastric cancer via recruiting EZH2 and activating PI3K/AKT pathway. J Cancer 11(13):3882–3892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Liu X et al (2019) LINC00665 Induces Acquired Resistance to Gefitinib through Recruiting EZH2 and Activating PI3K/AKT Pathway in NSCLC. Mol Ther Nucleic Acids 16:155–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Song L et al (2019) Long noncoding RNA OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATbeta/PI3K/AKT/mTOR signaling pathway by sponging the miR-340-5p. J Cell Biochem 120(6):9656–9666

    Article  CAS  PubMed  Google Scholar 

  56. Cui D et al (2020) Long non-coding RNA TRPM2-AS sponges microRNA-138-5p to activate epidermal growth factor receptor and PI3K/AKT signaling in non-small cell lung cancer. Ann Transl Med 8(20):1313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Li Z et al (2019) Knockdown of lncRNA-HOTAIR downregulates the drug-resistance of breast cancer cells to doxorubicin via the PI3K/AKT/mTOR signaling pathway. Exp Ther Med 18(1):435–442

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Polakis P (2012) Wnt signaling in cancer. Cold Spring Harb Perspect Biol 4(5):a008052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Chen Z et al (2020) The lncRNA-GAS5/miR-221-3p/DKK2 Axis Modulates ABCB1-Mediated Adriamycin Resistance of Breast Cancer via the Wnt/beta-Catenin Signaling Pathway. Mol Ther Nucleic Acids 19:1434–1448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chang HL et al (2020) Targeting the epigenetic non-coding RNA MALAT1/Wnt signaling axis as a therapeutic approach to suppress stemness and metastasis in hepatocellular carcinoma. Cells 9(4):1020. https://doi.org/10.3390/cells9041020

    Article  CAS  PubMed Central  Google Scholar 

  61. Gao H et al (2018) Long noncoding RNA H19 mediated the chemosensitivity of breast cancer cells via Wnt pathway and EMT process. Onco Targets Ther 11:8001–8012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wu KF et al (2017) H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/beta-catenin pathway. Exp Cell Res 350(2):312–317

    Article  CAS  PubMed  Google Scholar 

  63. Liu H et al (2016) Knockdown of Long Non-Coding RNA UCA1 Increases the Tamoxifen Sensitivity of Breast Cancer Cells through Inhibition of Wnt/beta-Catenin Pathway. PLoS One 11(12):e0168406

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Fan Y et al (2014) Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling. FEBS J 281(7):1750–1758

    Article  CAS  PubMed  Google Scholar 

  65. Guo F et al (2018) The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway. Exp Ther Med 15(6):4885–4889

    PubMed  PubMed Central  Google Scholar 

  66. Fang JY, Richardson BC (2005) The MAPK signalling pathways and colorectal cancer. Lancet Oncol 6(5):322–327

    Article  CAS  PubMed  Google Scholar 

  67. Liu S et al (2018) Overexpression of the lncRNA FER1L4 inhibits paclitaxel tolerance of ovarian cancer cells via the regulation of the MAPK signaling pathway. J Cell Biochem 121(2):2048

  68. Shen X et al (2019) Knockdown of long non-coding RNA PCAT-1 inhibits myeloma cell growth and drug resistance via p38 and JNK MAPK pathways. J Cancer 10(26):6502–6510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Guo JL et al (2020) LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway. Pathol Oncol Res 26(3):1757–1766

    Article  PubMed  Google Scholar 

  70. Pulido R et al (2014) A unified nomenclature and amino acid numbering for human PTEN. Sci Signal 7(332):pe15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Wang C et al (2020) Downregulation of LncRNA GAS5 promotes liver cancer proliferation and drug resistance by decreasing PTEN expression. Mol Genet Genomics 295(1):251–260

    Article  CAS  PubMed  Google Scholar 

  72. Xing S et al (2019) Deregulation of lncRNA-AC078883.3 and microRNA-19a is involved in the development of chemoresistance to cisplatin via modulating signaling pathway of PTEN/AKT. J Cell Physiol 234(12):22657–22665

    Article  CAS  PubMed  Google Scholar 

  73. Xiao H et al (2018) TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis. Cell Biosci 8:23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Fojo T, Coley HM (2007) The role of efflux pumps in drug-resistant metastatic breast cancer: new insights and treatment strategies. Clin Breast Cancer 7(10):749–756

    Article  CAS  PubMed  Google Scholar 

  75. Litman T et al (2001) From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell Mol Life Sci 58(7):931–959

    Article  CAS  PubMed  Google Scholar 

  76. Karki R et al (2013) betaIII-Tubulin: biomarker of taxane resistance or drug target? Expert Opin Ther Targets 17(4):461–472

    Article  CAS  PubMed  Google Scholar 

  77. Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2(1):48–58

    Article  CAS  PubMed  Google Scholar 

  78. Klein I, Sarkadi B, Varadi A (1999) An inventory of the human ABC proteins. Biochim Biophys Acta 1461(2):237–262

    Article  CAS  PubMed  Google Scholar 

  79. Gottesman MM, Ling V (2006) The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett 580(4):998–1009

    Article  CAS  PubMed  Google Scholar 

  80. Schinkel AH et al (1997) Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci U S A 94(8):4028–4033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Liu Q et al (2020) Identification of a lathyrane-type diterpenoid EM-E-11-4 as a novel paclitaxel resistance reversing agent with multiple mechanisms of action. Aging 12(4):3713–3729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kang Y et al (2020) Knockdown of LncRNA CRNDE suppresses proliferation and P-glycoprotein-mediated multidrug resistance in acute myelocytic leukemia through the Wnt/beta-catenin pathway. Biosci Rep 40(6):BSR20193450. https://doi.org/10.1042/BSR20193450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bakos E, Homolya L (2007) Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1). Pflugers Arch 453(5):621–41

    Article  CAS  PubMed  Google Scholar 

  84. Chen ZS et al (2005) Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol 67(2):545–557

    Article  CAS  PubMed  Google Scholar 

  85. Chen ZS et al (2003) Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol 63(2):351–8

    Article  CAS  PubMed  Google Scholar 

  86. Chu XY et al (2004) Transport of ethinylestradiol glucuronide and ethinylestradiol sulfate by the multidrug resistance proteins MRP1, MRP2, and MRP3. J Pharmacol Exp Ther 309(1):156–164

    Article  CAS  PubMed  Google Scholar 

  87. Hendig D et al (2008) Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis. Lab Invest 88(12):1303–1315

    Article  CAS  PubMed  Google Scholar 

  88. Homolya L, Varadi A, Sarkadi B (2003) Multidrug resistance-associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate. Biofactors 17(1–4):103–114

    Article  CAS  PubMed  Google Scholar 

  89. Russel FG, Koenderink JB, Masereeuw R (2008) Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules. Trends Pharmacol Sci 29(4):200–207

    Article  CAS  PubMed  Google Scholar 

  90. Sampath J et al (2002) Role of MRP4 and MRP5 in biology and chemotherapy. AAPS PharmSci 4(3):E14

    Article  CAS  PubMed  Google Scholar 

  91. Sharom FJ (2008) ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics 9(1):105–127

    Article  CAS  PubMed  Google Scholar 

  92. Zhou SF et al (2008) Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem 15(20):1981–2039

    Article  CAS  PubMed  Google Scholar 

  93. Jen J et al (2017) Oct4 transcriptionally regulates the expression of long non-coding RNAs NEAT1 and MALAT1 to promote lung cancer progression. Mol Cancer 16(1):104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Li S et al (2018) The lncRNA MALAT1 contributes to non-small cell lung cancer development via modulating miR-124/STAT3 axis. J Cell Physiol 233(9):6679–6688

    Article  CAS  PubMed  Google Scholar 

  95. Liu P et al (2017) The lncRNA MALAT1 acts as a competing endogenous RNA to regulate KRAS expression by sponging miR-217 in pancreatic ductal adenocarcinoma. Sci Rep 7(1):5186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Stone L (2017) Prostate cancer: Escaping enzalutamide: Malat1 contributes to resistance. Nat Rev Urol 14(8):450

    Article  PubMed  Google Scholar 

  97. Xie H et al (2017) LncRNA MALAT1 Inhibits Apoptosis and Promotes Invasion by Antagonizing miR-125b in Bladder Cancer Cells. J Cancer 8(18):3803–3811

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Zhang X, Hamblin MH, Yin KJ (2017) The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol 14(12):1705–1714

    Article  PubMed  PubMed Central  Google Scholar 

  99. Fang Z et al (2018) LncRNA-MALAT1 contributes to the cisplatin-resistance of lung cancer by upregulating MRP1 and MDR1 via STAT3 activation. Biomed Pharmacother 101:536–542

    Article  CAS  PubMed  Google Scholar 

  100. Wang L et al (2017) Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem-like cells via induction of lncRNA HOTAIR. Exp Ther Med 14(5):4773–4780

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wang ZH et al (1999) Bcl-2 and Bax proteins are nuclear matrix associated proteins. Anticancer Res 19(6B):5445–5449

    CAS  PubMed  Google Scholar 

  103. Yu S et al (2018) Galangin (GG) combined with cisplatin (DDP) to suppress human lung cancer by inhibition of STAT3-regulated NF-kappaB and Bcl-2/Bax signaling pathways. Biomed Pharmacother 97:213–224

    Article  CAS  PubMed  Google Scholar 

  104. Li X et al (2019) lncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis. Mol Ther Nucleic Acids 17:297–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132(1):27–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells tissues. Cell 147(4):728–741

    Article  CAS  PubMed  Google Scholar 

  107. Onorati AV et al (2018) Targeting autophagy in cancer. Cancer 124(16):3307–3318

    Article  PubMed  Google Scholar 

  108. Yang L et al (2017) Long non-coding RNAs involved in autophagy regulation. Cell Death Dis 8(10):e3073

    Article  PubMed  PubMed Central  Google Scholar 

  109. Yang Y et al (2018) Silencing of LncRNA-HOTAIR decreases drug resistance of Non-Small Cell Lung Cancer cells by inactivating autophagy via suppressing the phosphorylation of ULK1. Biochem Biophys Res Commun 497(4):1003–1010

    Article  CAS  PubMed  Google Scholar 

  110. Yadav B et al (2021) LncRNAs associated with glioblastoma: From transcriptional noise to novel regulators with a promising role in therapeutics. Mol Ther Nucleic Acids 24:728–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kansara S et al (2020) Mechanistic involvement of long non-coding RNAs in oncotherapeutics resistance in triple-negative breast cancer. Cells 9(6):1511

  112. Pal S, Garg M, Pandey AK (2020) Deciphering the mounting complexity of the p53 regulatory network in correlation to long non-coding RNAs (lncRNAs) in ovarian cancer. Cells 9(3):527

  113. Peng Y et al (2020) Long non-coding RNA: A recently accentuated molecule in chemoresistance in cancer. Cancer Metastasis Rev 39(3):825–835

    Article  CAS  PubMed  Google Scholar 

  114. Micallef I, Baron B (2021) The mechanistic roles of ncRNAs in promoting and supporting chemoresistance of colorectal cancer. Noncoding RNA 7(2):24

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This study was supported by Dr Linjiang Song, Postdoctoral Research Foundation of China (2019M653833XB).

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  1. Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, People’s Republic of China

    Jiaying He, Shaomi Zhu, Xin Liang, Qinxiu Zhang, Xiaohong Luo, Chi Liu & Linjiang Song

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  1. Jiaying He
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  2. Shaomi Zhu
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  3. Xin Liang
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Correspondence to Chi Liu or Linjiang Song.

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He, J., Zhu, S., Liang, X. et al. LncRNA as a multifunctional regulator in cancer multi-drug resistance. Mol Biol Rep 48, 1–15 (2021). https://doi.org/10.1007/s11033-021-06603-7

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