Skip to main content

The related miRNAs involved in doxorubicin resistance or sensitivity of various cancers: an update

Abstract

Doxorubicin (DOX) is an effective chemotherapy agent against a wide variety of tumors. However, intrinsic or acquired resistance diminishes the sensitivity of cancer cells to DOX, which leads to a cancer relapse and treatment failure. Resolutions to this challenge includes identification of the molecular pathways underlying DOX sensitivity/resistance and the development of innovative techniques to boost DOX sensitivity. DOX is classified as a Topoisomerase II poison, which is cytotoxic to rapidly dividing tumor cells. Molecular mechanisms responsible for DOX resistance include effective DNA repair and resumption of cell proliferation, deregulated development of cancer stem cell and epithelial to mesenchymal transition, and modulation of programmed cell death. MicroRNAs (miRNAs) have been shown to potentiate the reversal of DOX resistance as they have gene-specific regulatory functions in DOX-responsive molecular pathways. Identifying the dysregulation patterns of miRNAs for specific tumors following treatment with DOX facilitates the development of novel combination therapies, such as nanoparticles harboring miRNA or miRNA inhibitors to eventually prevent DOX-induced chemoresistance. In this article, we summarize recent findings on the role of miRNAs underlying DOX sensitivity/resistance molecular pathways. Also, we provide latest strategies for utilizing deregulated miRNA patterns as biomarkers or miRNAs as tools to overcome chemoresistance and enhance patient’s response to DOX treatment.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Availability of data and materials

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

DOX:

Doxorubicin, Adriamycin

TOP2:

Topoisomerase II

DDR:

DNA damage response

CSC:

Cancer stem cell

EMT:

Epithelial to mesenchymal transition

miRNAs:

MicroRNAs

WHO:

World Health Organization

MDR:

Multidrug resistance

DSBs:

DNA double-strand breaks

PARP1:

Poly ADP-ribose polymerase1

HDAC1:

Histone deacetylase1

BMI1:

B-lymphoma Moloney murine leukemia virus insertion region-1 protein

FANCF:

Fanconi anemia complementation group F

CDIs:

Cyclin-dependent kinase inhibitors

CDKs:

Cyclin-dependent kinases

PANK1:

Panto-therate kinase-1

AURKA:

Aurora kinase A

PI3K:

Phosphoinositide-3 kinase

mTOR:

Mechanistic target of rapamycin

MAPK:

Mitogen-activated protein kinase

VEGFA:

Vascular endothelial growth factor A

FGF2:

Fibroblast growth factor2

TAC:

Docetaxol, doxorubicin plus cisplatin

PKB:

Protein kinase B

CML:

Chronic myeloid leukemia

PTEN:

Phosphatase and tensin homolog

AML:

Acute myeloid leukemia

KRAS:

Kirstin rat sarcoma viral oncogene protein

MAPK7:

Mitogen-activated protein kinase7

MEKK1:

MAP/ERK kinase kinase1

RUNX2:

Runt related transcription factor 2

TFAP4:

Transcription factor activated enhancer-binding proten4

NAMPT:

Nicotinamide phosphoribosyltransferase

PPIA:

Peptidyl poly-isomerase A

ROS:

Reactive oxygen species

Bcl-2:

B-cell lymphoma-2

Bcl-2 Like1:

Apoptotic Bcl-2 members including Bcl2L1

NTSR1:

Glioblastoma neurotensin receptor 1

MCL1:

Myeloid leukemia 1

DISC:

Death-inducing signaling complex

cFLIP:

Cellular FLICE-like inhibitory

SIRT1:

Silent information regulator 1

BIM:

Bcl-2 interacting mediator

BLID:

BH3-like –motif-containing protein

FOX:

Forkedhead box

FOXO1:

FOX class O1

FOXP2:

FOX class P2

FOXO3:

FOX class O3

FADD:

Fas-associated death domain

ULK1:

Unc51-like autophagy-activating kinase

ATGs:

Autophagy-related genes

LAPTM4B:

Lysosomal protein transmembrane 4 beta

ATG16L1:

Autophagy related 16-like-1

HMGN5:

High-mobility group nucleosome domain 5

HMGB1:

High-mobility group box1

P-glycoprotein:

P-gp

MDR1:

Multidrug resistance protein1

CAR:

Constitutive androstane receptor

ZNRD1:

Zink ribbon domain-containing

MRP1:

Multidrug resistance-associated protein1

SPIN1:

Spindlin1

Wnt:

Wingless

p-β-catenin:

Phospho-β-catenin

NEAT1:

Nuclear enriched abundant transcript1

Sox7:

Sex-determining region Y-box7

PKD1:

Protein kinase D1

GSK3:

Glycogen synthase kinase 3

YB1:

Factor Y box-binding protein 1

PD-L1:

Programmed cell death ligand 1

TWIST1:

Twist-related protein 1

ZEB1/2:

Zinc finger E-box-binding homeobox ½

eIF5A2:

Eukaryotic translational initiation factor 5 A2

STMN1:

Statmin1

OPN:

Osteopontin

MDR:

Multidrug resistance

USP9X:

Ubiquitin specific peptidase 9 X-linked

NLS:

Nuclear localization signal

References

  1. 1.

    Bray F et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  Google Scholar 

  2. 2.

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

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  3. 3.

    Delgir S et al (2021) The pathways related to glutamine metabolism, glutamine inhibitors and their implication for improving the efficiency of chemotherapy in triple-negative breast cancer. Mutat Res 787:108366

    CAS  Article  Google Scholar 

  4. 4.

    Swift LP et al (2006) Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell death. Cancer Res 66(9):4863–4871

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Sikora K et al (1999) Essential drugs for cancer therapy: a World Health Organization consultation. Ann Oncol 10(4):385–390

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Denard B, Lee C, Ye J (2012) Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1. Elife 1:e00090

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  7. 7.

    Cao WQ et al (2019) Enhanced anticancer efficiency of doxorubicin against human glioma by natural borneol through triggering ROS-mediated signal. Biomed Pharmacother 118:109261

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Li Q et al (2020) Rac1 activates non-oxidative pentose phosphate pathway to induce chemoresistance of breast cancer. Nat Commun 11(1):1456

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Wang H, Huang Y (2020) Combination therapy based on nano codelivery for overcoming cancer drug resistance. Med Drug Discov 6:100024

    Article  Google Scholar 

  10. 10.

    Du F et al (2019) miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4. Cell Death Dis 10(12):922

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Choi YH, Yu AM (2014) ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr Pharm Des 20(5):793–807

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Cox J, Weinman S (2016) Mechanisms of doxorubicin resistance in hepatocellular carcinoma. Hepat Oncol 3(1):57–59

    PubMed  Article  Google Scholar 

  13. 13.

    Wang Y et al (2020) Berberine reverses doxorubicin resistance by inhibiting autophagy through the PTEN/Akt/mTOR signaling pathway in breast cancer. Onco Targets Ther 13:1909–1919

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Chen DR et al (2014) Mesenchymal stem cell-induced doxorubicin resistance in triple negative breast cancer. Biomed Res Int 204:32161

    Google Scholar 

  15. 15.

    Pfitzer L et al (2019) Targeting actin inhibits repair of doxorubicin-induced DNA damage: a novel therapeutic approach for combination therapy. Cell Death Dis 10(4):302

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  16. 16.

    Christowitz C et al (2019) Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model. BMC Cancer 19(1):757

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  17. 17.

    Zare M et al (2018) Aberrant miRNA promoter methylation and EMT-involving miRNAs in breast cancer metastasis: diagnosis and therapeutic implications. J Cell Physiol 233(5):3729–3744

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Peng Y, Croce CM (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1:15004

    PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Ilkhani K et al (2021) Clinical and in silico outcomes of the expression of miR-130a-5p and miR-615-3p in tumor compared with non-tumor adjacent tissues of patients with BC. Anticancer Agents Med Chem 21(7):927–935

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Magee P, Shi L, Garofalo M (2015) Role of microRNAs in chemoresistance. Ann Transl Med 3(21):332

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Simonson B, Das S (2015) MicroRNA therapeutics: the next magic bullet? Mini Rev Med Chem 15(6):467–474

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Ilkhani K et al (2021) The engaged role of tumor microenvironment in cancer metabolism: focusing on cancer-associated fibroblast and exosome mediators. Anticancer Agents Med Chem 21(2):254–266

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Gorini S et al (2018) Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxid Med Cell Longev 2018:7582730

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. 24.

    Pubchem, Doxorubicin 2021, National Center for Biotechnology Information (2020) PubChem compound summary for CID 31703, doxorubicin. Retrieved 18 Nov 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Doxorubicin.

  25. 25.

    Edwardson DW et al (2015) Role of drug metabolism in the cytotoxicity and clinical efficacy of anthracyclines. Curr Drug Metab 16(6):412–426

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Kluza J et al (2004) Mitochondrial proliferation during apoptosis induced by anticancer agents: effects of doxorubicin and mitoxantrone on cancer and cardiac cells. Oncogene 23(42):7018–7030

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Butowska K et al (2021) Polymeric nanocarriers: a transformation in doxorubicin therapies. Materials (Basel) 14(9):2135

    Article  Google Scholar 

  28. 28.

    Shivakumar P et al (2012) A study on the toxic effects of Doxorubicin on the histology of certain organs. Toxicol Int 19(3):241–244

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Shankaranarayanan JS et al (2016) doxorubicin conjugated to immunomodulatory anticancer lactoferrin displays improved cytotoxicity overcoming prostate cancer chemo resistance and inhibits tumour development in TRAMP mice. Sci Rep 6:32062

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Sacco G et al (2003) Chronic cardiotoxicity of anticancer anthracyclines in the rat: role of secondary metabolites and reduced toxicity by a novel anthracycline with impaired metabolite formation and reactivity. Br J Pharmacol 139(3):641–651

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Tayeh Z, Ofir R (2018) Asteriscus graveolens extract in combination with cisplatin/etoposide/doxorubicin suppresses lymphoma cell growth through induction of caspase-3 dependent apoptosis. Int J Mol Sci 19(8):2219

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  32. 32.

    Xu F et al (2017) MiR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma. Cancer Med 6(3):651–661

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Kopp F et al (2012) miR-200c sensitizes breast cancer cells to doxorubicin treatment by decreasing TrkB and Bmi1 expression. PLoS ONE 7(11):e50469

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Ma J, Dong C, Ji C (2010) MicroRNA and drug resistance. Cancer Gene Ther 17(8):523–531

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Zhang B et al (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302(1):1–12

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    He M et al (2016) MicroRNAs, DNA damage response, and cancer treatment. Int J Mol Sci 17(12):2087

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  37. 37.

    Jin F et al (2017) MiR-26 enhances chemosensitivity and promotes apoptosis of hepatocellular carcinoma cells through inhibiting autophagy. Cell Death Dis 8(1):2540

    Article  CAS  Google Scholar 

  38. 38.

    Talebian S et al (2020) The role of epigenetics and non-coding RNAs in autophagy: A new perspective for thorough understanding. Mech Ageing Dev 190:111309

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Kubiliute R et al (2016) Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line. Med (Kaunas) 52(5):298–306

    Google Scholar 

  40. 40.

    Borges HL, Linden R, Wang JY (2008) DNA damage-induced cell death: lessons from the central nervous system. Cell Res 18(1):17–26

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Yang F, Kemp CJ, Henikoff S (2015) Anthracyclines induce double-strand DNA breaks at active gene promoters. Mutat Res 773:9–15

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Wang Y, Taniguchi T (2013) MicroRNAs and DNA damage response: implications for cancer therapy. Cell Cycle 12(1):32–42

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Davalli P et al (2018) Targeting oxidatively induced DNA damage response in cancer: opportunities for novel cancer therapies. Oxid Med Cell Longev 2018:2389523

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  44. 44.

    Wu Q, Ketley RF, Gullerova M (2020) Jack of all trades? The versatility of RNA in DNA double-strand break repair. Essays Biochem 64(5):721–735

    Article  Google Scholar 

  45. 45.

    Zhang X, Lu X (2011) Posttranscriptional regulation of miRNAs in the DNA damage response. RNA Biol 8(6):960–963

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Gajda E et al (2021) The role of miRNA-7 in the biology of cancer and modulation of drug resistance. Pharmaceut (Basel) 14(2):149

    CAS  Article  Google Scholar 

  47. 47.

    Lai J et al (2019) MiR-7-5p-mediated downregulation of PARP1 impacts DNA homologous recombination repair and resistance to doxorubicin in small cell lung cancer. BMC Cancer 19(1):602

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  48. 48.

    Caron MC et al (2019) Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks. Nat Commun 10(1):2954

    PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Shen Q et al (2014) Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin. FEBS Lett 588(1):184–191

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Ismail IH et al (2010) BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair. J Cell Biol 191(1):45–60

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Patel N et al (2017) Erratum: miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair and breast cancer cell sensitivity to doxorubicin. Sci Rep 7(1):12932

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. 52.

    Menon V, Povirk L (2014) Involvement of p53 in the repair of DNA double strand breaks: multifaceted Roles of p53 in homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Subcell Biochem 85:321–336

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Fischer M (2017) Census and evaluation of p53 target genes. Oncogene 36(28):3943–3956

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Tsuchiya N et al (2011) Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res 71(13):4628–4639

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Ivanovska I et al (2008) MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol 28(7):2167–2174

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Lin S et al (2019) Intrinsic adriamycin resistance in p53-mutated breast cancer is related to the miR-30c/FANCF/REV1-mediated DNA damage response. Cell Death Dis 10(9):666

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  57. 57.

    Gao X et al (2019) MicroRNA-16 sensitizes drug-resistant breast cancer cells to Adriamycin by targeting Wip1 and Bcl-2. Oncol Lett 18(3):2897–2906

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Zhang X et al (2010) Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res 70(18):7176–7186

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Hall AE et al (2016) The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration. Cell Death Dis 7:e2184

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. 60.

    Fornari F et al (2009) MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 69(14):5761–5767

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Lim S, Kaldis P (2013) Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 140(15):3079–3093

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Johnson N, Shapiro GI (2010) Cyclin-dependent kinases (cdks) and the DNA damage response: rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors. Expert Opin Ther Targets 14(11):1199–1212

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  63. 63.

    Tormo E et al (2019) The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors. Sci Rep 9(1):5316

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  64. 64.

    Xu YY et al (2019) MicroRNA-26a inhibits multiple myeloma cell growth by suppressing cyclin-dependent kinase 6 expression. Kaohsiung J Med Sci 35(5):277–283

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Bohlig L, Friedrich M, Engeland K (2011) p53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins. Nucleic Acids Res 39(2):440–453

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Yuan YL et al (2019) MiR-26a-5p inhibits cell proliferation and enhances doxorubicin sensitivity in HCC cells via targeting AURKA. Technol Cancer Res Treat 18:1533033819851833

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Demel HR et al (2015) Effects of topoisomerase inhibitors that induce DNA damage response on glucose metabolism and PI3K/Akt/mTOR signaling in multiple myeloma cells. Am J Cancer Res 5(5):1649–1664

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    De P et al (2014) Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia 16(1):43–72

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Wei F, Yan J, Tang D (2011) Extracellular signal-regulated kinases modulate DNA damage response—a contributing factor to using MEK inhibitors in cancer therapy. Curr Med Chem 18(35):5476–5482

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Hu M et al (2019) MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review). Oncol Rep 41(3):1439–1454

    CAS  PubMed  Google Scholar 

  71. 71.

    Hu Y et al (2016) miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell Death Dis 7(6):e2291

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. 72.

    Zhao Z et al (2014) Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation. Cancer Biol Ther 15(10):1404–1412

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Yu Z et al (2014) miR-17/20 sensitization of breast cancer cells to chemotherapy-induced apoptosis requires Akt1. Oncotarget 5(4):1083–1090

    PubMed  PubMed Central  Article  Google Scholar 

  74. 74.

    Yan ZX et al (2015) MicroRNA181a is overexpressed in T-Cell leukemia/lymphoma and related to chemoresistance. Biomed Res Int 2015:197241

    PubMed  PubMed Central  Google Scholar 

  75. 75.

    Zhao L et al (2016) Upregulation of miR-181c inhibits chemoresistance by targeting ST8SIA4 in chronic myelocytic leukemia. Oncotarget 7(37):60074–60086

    PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Xiao Q et al (2017) MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo-resistance via ZNRF2. Oncotarget 8(21):34678–34686

    PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Astuti I et al (2019) MicroRNA-21 and PTEN expression levels are negatively correlated in doxorubicin resistant MCF-7 breast cancer cell line

  78. 78.

    Tao J et al (2011) microRNA-21 modulates cell proliferation and sensitivity to doxorubicin in bladder cancer cells. Oncol Rep 25(6):1721–1729

    CAS  PubMed  Google Scholar 

  79. 79.

    Liu T, Guo J, Zhang X (2019) MiR-202-5p/PTEN mediates doxorubicin-resistance of breast cancer cells via PI3K/Akt signaling pathway. Cancer Biol Ther 20(7):989–998

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  80. 80.

    Miao Y et al (2017) MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway. Sci Rep 7:41942

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Yin Y et al (2020) MicroRNA-221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling. Cancer Med 9(4):1544–1552

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. 82.

    Wang DD et al (2016) miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27(kip1) pathway. Tumour Biol 37(11):15315–15324

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Abrams SL et al (2010) The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy. Cell Cycle 9(9):1781–1791

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. 84.

    Li L et al (2016) The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol Lett 12(5):3045–3050

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  85. 85.

    Xiao Y et al (2017) MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS. Oncol Lett 13(6):4986–4994

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Liu M et al (2020) MicroRNA-187 suppresses the proliferation migration and invasion of human osteosarcoma cells by targeting MAPK7. J BUON 25(1):472–478

    PubMed  Google Scholar 

  87. 87.

    Zhao L et al (2016) MiR-302a/b/c/d cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein(P-gp) by targeting MAP/ERK kinase kinase 1 (MEKK1). J Exp Clin Cancer Res 35:25

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  88. 88.

    Ling Z et al (2020) MicroRNA-150 functions as a tumor suppressor and sensitizes osteosarcoma to doxorubicin-induced apoptosis by targeting RUNX2. Exp Ther Med 19(1):481–488

    CAS  PubMed  Google Scholar 

  89. 89.

    Wang YF et al (2019) MicroRNA-608 promotes apoptosis in non-small cell lung cancer cells treated with doxorubicin through the inhibition of TFAP4. Front Genet 10:809

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  90. 90.

    Bolandghamat Pour Z et al (2019) Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin. BMC Cancer 19(1):1027

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  91. 91.

    Zhang Y et al (2019) miRNA-192-5p impacts the sensitivity of breast cancer cells to doxorubicin via targeting peptidylprolyl isomerase A. Kaohsiung J Med Sci 35(1):17–23

    PubMed  Article  CAS  Google Scholar 

  92. 92.

    Sun FD et al (2018) MicroRNA-574 enhances doxorubicin resistance through down-regulating SMAD4 in breast cancer cells. Eur Rev Med Pharmacol Sci 22(5):1342–1350

    PubMed  Google Scholar 

  93. 93.

    Chen J et al (2018) miR215p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3. Int J Mol Med 41(4):1855–1866

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    L’Ecuyer T et al (2006) DNA damage is an early event in doxorubicin-induced cardiac myocyte death. Am J Physiol Heart Circ Physiol 291(3):H1273–H1280

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Luzhna L et al (2013) Molecular mechanisms of radiation resistance in doxorubicin-resistant breast adenocarcinoma cells. Int J Oncol 42(5):1692–1708

    CAS  PubMed  Article  Google Scholar 

  96. 96.

    An X et al (2017) Regulation of multidrug resistance by microRNAs in anti-cancer therapy. Acta Pharm Sin B 7(1):38–51

    PubMed  Article  Google Scholar 

  97. 97.

    Mognato M, Celotti L (2015) MicroRNAs used in combination with anti-cancer treatments can enhance therapy efficacy. Mini Rev Med Chem 15(13):1052–1062

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. 98.

    Pearce MC et al (2018) Induction of apoptosis and suppression of tumor growth by Nur77-derived Bcl-2 converting peptide in chemoresistant lung cancer cells. Oncotarget 9(40):26072–26085

    PubMed  PubMed Central  Article  Google Scholar 

  99. 99.

    Kale J, Osterlund EJ, Andrews DW (2018) BCL-2 family proteins: changing partners in the dance towards death. Cell Death Differ 25(1):65–80

    CAS  PubMed  Article  Google Scholar 

  100. 100.

    Mao F et al (2019) miR-149 inhibits cell proliferation and enhances chemosensitivity by targeting CDC42 and BCL2 in neuroblastoma. Cancer Cell Int 19:357

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. 101.

    Verdoodt B et al (2013) MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer. Int J Oncol 43(1):307–314

    CAS  PubMed  Article  Google Scholar 

  102. 102.

    Pan Y et al (2014) Regulation of BGC-823 cell sensitivity to adriamycin via miRNA-135a-5p. Oncol Rep 32(6):2549–2556

    CAS  PubMed  Article  Google Scholar 

  103. 103.

    Lin BC et al (2016) MicroRNA-184 modulates doxorubicin resistance in osteosarcoma cells by targeting BCL2L1. Med Sci Monit 22:1761–1765

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. 104.

    Dong Z et al (2017) Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma. Br J Cancer 116(12):1572–1584

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  105. 105.

    Long J et al (2015) miR-193b modulates resistance to doxorubicin in human breast cancer cells by downregulating MCL-1. Biomed Res Int 2015:373574

    PubMed  PubMed Central  Google Scholar 

  106. 106.

    Osaki S et al (2016) Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas. Sci Rep 6:28953

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. 107.

    Kim EA et al (2016) Inhibition of c-FLIPL expression by miRNA-708 increases the sensitivity of renal cancer cells to anti-cancer drugs. Oncotarget 7(22):31832–31846

    PubMed  PubMed Central  Article  Google Scholar 

  108. 108.

    Shu Y et al (2017) MiR-204 enhances mitochondrial apoptosis in doxorubicin-treated prostate cancer cells by targeting SIRT1/p53 pathway. Oncotarget 8(57):97313–97322

    PubMed  PubMed Central  Article  Google Scholar 

  109. 109.

    Zheng Y et al (2016) MiR-181b promotes chemoresistance in breast cancer by regulating Bim expression. Oncol Rep 35(2):683–690

    CAS  PubMed  Article  Google Scholar 

  110. 110.

    Dai H et al. (2019) MicroRNA-222 promotes drug resistance to doxorubicin in breast cancer via regulation of miR-222/bim pathway. Biosci Rep 39(7)

  111. 111.

    Sun Y et al (2016) MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma. Sci Rep 6:34238

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  112. 112.

    Xu YC et al (2018) A novel mechanism of doxorubicin resistance and tumorigenesis mediated by MicroRNA-501-5p-suppressed BLID. Mol Ther Nucleic Acids 12:578–590

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  113. 113.

    Iwai N et al (2018) Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma. Int J Oncol 53(1):237–245

    CAS  PubMed  Google Scholar 

  114. 114.

    Reza A et al (2017) MicroRNA-7641 is a regulator of ribosomal proteins and a promising targeting factor to improve the efficacy of cancer therapy. Sci Rep 7(1):8365

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  115. 115.

    Fu Z, Tindall DJ (2008) FOXOs, cancer and regulation of apoptosis. Oncogene 27(16):2312–2319

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  116. 116.

    Han CY et al (2008) Role of FoxO1 activation in MDR1 expression in adriamycin-resistant breast cancer cells. Carcinogenesis 29(9):1837–1844

    CAS  PubMed  Article  Google Scholar 

  117. 117.

    Soheilifar MH et al. (2020) Concomitant overexpression of mir-182–5p and mir-182–3p raises the possibility of IL-17-producing Treg formation in breast cancer by targeting CD3d, ITK, FOXO1, and NFATs: a meta-analysis and experimental study. Cancer Sci

  118. 118.

    Lang C et al (2018) MicroRNA-96 expression induced by low-dose cisplatin or doxorubicin regulates chemosensitivity, cell death and proliferation in gastric cancer SGC7901 cells by targeting FOXO1. Oncol Lett 16(3):4020–4026

    PubMed  PubMed Central  Google Scholar 

  119. 119.

    Wang H et al (2019) Downregulation of miR-222-3p reverses doxorubicin-resistance in LoVo cells through upregulating forkhead box protein P2 (FOXP2) protein. Med Sci Monit 25:2169–2178

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  120. 120.

    Pang X et al (2019) Foxo3a-dependent miR-633 regulates chemotherapeutic sensitivity in gastric cancer by targeting Fas-associated death domain. RNA Biol 16(2):233–248

    PubMed  PubMed Central  Article  Google Scholar 

  121. 121.

    Seo HA et al (2019) MicroRNA-based combinatorial cancer therapy: effects of MicroRNAs on the efficacy of anti-cancer therapies. Cells 9(1):29

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  122. 122.

    Zhou Y et al (2019) miR-223 overexpression inhibits doxorubicin-induced autophagy by targeting FOXO3a and reverses chemoresistance in hepatocellular carcinoma cells. Cell Death Dis 10(11):843

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  123. 123.

    Chavez-Dominguez R et al (2020) The double-edge sword of autophagy in cancer: from tumor suppression to pro-tumor activity. Front Oncol 10:578418

    PubMed  PubMed Central  Article  Google Scholar 

  124. 124.

    Denton D, Kumar S (2019) Autophagy-dependent cell death. Cell Death Differ 26(4):605–616

    CAS  PubMed  Article  Google Scholar 

  125. 125.

    Soni M et al (2018) Autophagy, cell viability, and chemoresistance are regulated by miR-489 in breast cancer. Mol Cancer Res 16(9):1348–1360

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  126. 126.

    Zhu K et al (2020) LncRNA Sox2OT-V7 promotes doxorubicin-induced autophagy and chemoresistance in osteosarcoma via tumor-suppressive miR-142/miR-22. Aging (Albany NY) 12(8):6644–6666

    CAS  Article  Google Scholar 

  127. 127.

    Chen R et al (2017) MicroRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma. Mol Med Rep 15(3):1326–1334

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  128. 128.

    Xu R et al (2016) MicroRNA-30a downregulation contributes to chemoresistance of osteosarcoma cells through activating Beclin-1-mediated autophagy. Oncol Rep 35(3):1757–1763

    CAS  PubMed  Article  Google Scholar 

  129. 129.

    Cui X et al (2020) MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma. Transl Oncol 13(10):100805

    PubMed  PubMed Central  Article  Google Scholar 

  130. 130.

    Wei R et al (2016) miR-140–5p attenuates chemotherapeutic drug-induced cell death by regulating autophagy through inositol 1,4,5-trisphosphate kinase 2 (IP3k2) in human osteosarcoma cells. Biosci Rep 36(5)

  131. 131.

    Chang Z et al (2014) Blocked autophagy by miR-101 enhances osteosarcoma cell chemosensitivity in vitro. Sci World J 14:794756

    Google Scholar 

  132. 132.

    Meng Y et al (2017) MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy. Sci Rep 7(1):416

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  133. 133.

    Liang L et al (2020) MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1. Acta Pharm Sin B 10(6):1036–1046

    CAS  PubMed  Article  Google Scholar 

  134. 134.

    Muriithi W et al (2020) ABC transporters and the hallmarks of cancer: roles in cancer aggressiveness beyond multidrug resistance. Cancer Biol Med 17(2):253–269

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  135. 135.

    Ariana M et al (2018) The diversity in the expression profile of caveolin II transcripts, considering its new transcript in breast cancer. J Cell Biochem 119(2):2168–2178

    CAS  PubMed  Article  Google Scholar 

  136. 136.

    Lee CY et al (2016) The influence of a caveolin-1 mutant on the function of P-glycoprotein. Sci Rep 6:20486

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. 137.

    Zou Z et al (2017) miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression. J Cell Mol Med 21(9):1929–1943

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  138. 138.

    Takwi AA et al (2014) miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells. Oncogene 33(28):3717–3729

    CAS  PubMed  Article  Google Scholar 

  139. 139.

    Shang Y et al (2014) miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene 33(25):3267–3276

    CAS  PubMed  Article  Google Scholar 

  140. 140.

    Xu Y et al (2013) Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance. PLoS ONE 8(11):82062

    Article  CAS  Google Scholar 

  141. 141.

    Chen J et al (2012) Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer. Med Oncol 29(4):2527–2534

    CAS  PubMed  Article  Google Scholar 

  142. 142.

    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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  143. 143.

    Bao L et al (2012) Increased expression of P-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298. Am J Pathol 180(6):2490–2503

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  144. 144.

    Liang Z et al (2010) Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem Pharmacol 79(6):817–824

    CAS  PubMed  Article  Google Scholar 

  145. 145.

    Gao M et al (2016) miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1. Oncotarget 7(37):59714–59726

    PubMed  PubMed Central  Article  Google Scholar 

  146. 146.

    Lu L et al (2015) MicroRNA-134 modulates resistance to doxorubicin in human breast cancer cells by downregulating ABCC1. Biotechnol Lett 37(12):2387–2394

    CAS  PubMed  Article  Google Scholar 

  147. 147.

    Pan YZ et al (2013) Small nucleolar RNA-derived microRNA hsa-miR-1291 modulates cellular drug disposition through direct targeting of ABC transporter ABCC1. Drug Metab Dispos 41(10):1744–1751

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  148. 148.

    Hou H et al (2017) miR-33a expression sensitizes Lgr5+ HCC-CSCs to doxorubicin via ABCA1. Neoplasma 64(1):81–91

    CAS  PubMed  Article  Google Scholar 

  149. 149.

    Zheng D et al (2015) MicroRNA-299-3p promotes the sensibility of lung cancer to doxorubicin through directly targeting ABCE1. Int J Clin Exp Pathol 8(9):10072–10081

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150.

    Chen X, Wang YW, Gao P (2018) SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer. J Exp Clin Cancer Res 37(1):100

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  151. 151.

    Khan AQ et al. (2019) Role of miRNA-regulated cancer stem cells in the pathogenesis of human malignancies. Cells 8(8)

  152. 152.

    Mohammed MK et al (2016) Wnt/beta-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance. Genes Dis 3(1):11–40

    PubMed  PubMed Central  Article  Google Scholar 

  153. 153.

    Guo Y et al (2018) Non-coding RNA NEAT1/miR-214-3p contribute to doxorubicin resistance of urothelial bladder cancer preliminary through the Wnt/beta-catenin pathway. Cancer Manag Res 10:4371–4380

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  154. 154.

    Zheng Z et al (2016) MicroRNA-452 promotes stem-like cells of hepatocellular carcinoma by inhibiting Sox7 involving Wnt/beta-catenin signaling pathway. Oncotarget 7(19):28000–28012

    PubMed  PubMed Central  Article  Google Scholar 

  155. 155.

    Kim do Y et al (2016) A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/beta-catenin signaling in breast cancer. Oncotarget 7(12):14791–14802

    PubMed  Article  Google Scholar 

  156. 156.

    Park EY et al (2014) Targeting of miR34a-NOTCH1 axis reduced breast cancer stemness and chemoresistance. Cancer Res 74(24):7573–7582

    CAS  PubMed  Article  Google Scholar 

  157. 157.

    Xu M et al (2015) miR-382 inhibits osteosarcoma metastasis and relapse by targeting Y box-binding protein 1. Mol Ther 23(1):89–98

    CAS  PubMed  Article  Google Scholar 

  158. 158.

    Gao L et al (2019) MiR-873/PD-L1 axis regulates the stemness of breast cancer cells. EBioMedicine 41:395–407

    PubMed  PubMed Central  Article  Google Scholar 

  159. 159.

    Wang SS et al (2015) Links between cancer stem cells and epithelial-mesenchymal transition. Onco Targets Ther 8:2973–2980

    CAS  PubMed  PubMed Central  Google Scholar 

  160. 160.

    Dudas J et al (2020) Epithelial to mesenchymal transition: a mechanism that fuels cancer radio/chemoresistance. Cells 9(2)

  161. 161.

    Long L et al (2019) ZEB1 mediates doxorubicin (Dox) resistance and mesenchymal characteristics of hepatocarcinoma cells. Exp Mol Pathol 106:116–122

    CAS  PubMed  Article  Google Scholar 

  162. 162.

    Kwok GTY et al (2019) microRNA-431 as a chemosensitizer and potentiator of drug activity in adrenocortical carcinoma. Oncologist 24(6):e241–e250

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  163. 163.

    Lee JW et al (2018) MicroRNA-708-3p mediates metastasis and chemoresistance through inhibition of epithelial-to-mesenchymal transition in breast cancer. Cancer Sci 109(5):1404–1413

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  164. 164.

    Jin Z et al (2016) MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition. Eur Rev Med Pharmacol Sci 20(6):1080–1086

    CAS  PubMed  Google Scholar 

  165. 165.

    Hu SH et al (2016) miR-760 mediates chemoresistance through inhibition of epithelial mesenchymal transition in breast cancer cells. Eur Rev Med Pharmacol Sci 20(23):5002–5008

    PubMed  Google Scholar 

  166. 166.

    Zhou Y et al (2014) The miR-106b~25 cluster promotes bypass of doxorubicin-induced senescence and increase in motility and invasion by targeting the E-cadherin transcriptional activator EP300. Cell Death Differ 21(3):462–474

    CAS  PubMed  Article  Google Scholar 

  167. 167.

    Chu S et al (2017) miR-93 and PTEN: key regulators of doxorubicin-resistance and EMT in breast cancer. Oncol Rep 38(4):2401–2407

    CAS  PubMed  Article  Google Scholar 

  168. 168.

    Tryndyak VP, Beland FA, Pogribny IP (2010) E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer 126(11):2575–2583

    CAS  PubMed  Google Scholar 

  169. 169.

    Chen Y et al (2013) miRNA-200c increases the sensitivity of breast cancer cells to doxorubicin through the suppression of E-cadherin-mediated PTEN/Akt signaling. Mol Med Rep 7(5):1579–1584

    CAS  PubMed  Article  Google Scholar 

  170. 170.

    Alam F et al (2017) The role of p53-microRNA 200-Moesin axis in invasion and drug resistance of breast cancer cells. Tumour Biol 39(9):1010428317714634

    PubMed  Article  CAS  Google Scholar 

  171. 171.

    Bockhorn J et al (2013) MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat Commun 4:1393

    PubMed  Article  CAS  Google Scholar 

  172. 172.

    Guan X et al (2019) MicroRNA-33a-5p overexpression sensitizes triple-negative breast cancer to doxorubicin by inhibiting eIF5A2 and epithelial-mesenchymal transition. Oncol Lett 18(6):5986–5994

    CAS  PubMed  PubMed Central  Google Scholar 

  173. 173.

    Tu C et al (2019) MicroRNA-383 inhibits doxorubicin resistance in hepatocellular carcinoma by targeting eukaryotic translation initiation factor 5A2. J Cell Mol Med 23(11):7190–7199

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  174. 174.

    Li Y et al (2018) MiR-770 suppresses the chemo-resistance and metastasis of triple negative breast cancer via direct targeting of STMN1. Cell Death Dis 9(1):14

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  175. 175.

    Tao L et al (2020) MiR-451a attenuates doxorubicin resistance in lung cancer via suppressing epithelialmesenchymal transition (EMT) through targeting c-Myc. Biomed Pharmacother 125:109962

    CAS  PubMed  Article  Google Scholar 

  176. 176.

    Wang J et al (2017) Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. Oncotarget 8(48):84559–84571

    PubMed  PubMed Central  Article  Google Scholar 

  177. 177.

    Zhang Y, Wang Z, Gemeinhart RA (2013) Progress in microRNA delivery. J Control Release 172(3):962–974

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  178. 178.

    Salzano G et al (2016) Mixed nanosized polymeric micelles as promoter of doxorubicin and miRNA-34a co-delivery triggered by dual stimuli in tumor tissue. Small 12(35):4837–4848

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  179. 179.

    Zhao Y et al (2015) Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth. Biochem Pharmacol 98(4):602–613

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  180. 180.

    Lou G et al (2020) MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway. J Exp Clin Cancer Res 39(1):4

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  181. 181.

    Gajda E et al (2020) Combinatory treatment with miR-7–5p and drug-loaded cubosomes effectively impairs cancer cells. Int J Mol Sci 21(14)

  182. 182.

    Chen W et al (2019) Delivery of miR-212 by chimeric peptide-condensed supramolecular nanoparticles enhances the sensitivity of pancreatic ductal adenocarcinoma to doxorubicin. Biomaterials 192:590–600

    CAS  PubMed  Article  Google Scholar 

  183. 183.

    Xue H et al (2017) Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma. Int J Nanomed 12:5271–5287

    CAS  Article  Google Scholar 

  184. 184.

    Fan YP et al (2017) MiR-375 and doxorubicin co-delivered by liposomes for combination therapy of hepatocellular carcinoma. Mol Ther Nucleic Acids 7:181–189

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  185. 185.

    Gong C et al (2019) Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy. J Nanobiotechnol 17(1):93

    Article  CAS  Google Scholar 

  186. 186.

    Yoo B et al (2015) Combining miR-10b-targeted nanotherapy with low-dose doxorubicin elicits durable regressions of metastatic breast cancer. Cancer Res 75(20):4407–4415

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  187. 187.

    Rui M et al (2017) Simultaneous delivery of anti-miR21 with doxorubicin prodrug by mimetic lipoprotein nanoparticles for synergistic effect against drug resistance in cancer cells. Int J Nanomed 12:217–237

    CAS  Article  Google Scholar 

  188. 188.

    Safi A et al (2021) miRNAs modulate the dichotomy of cisplatin resistance or sensitivity in breast cancer: an update of therapeutic implications. Anticancer Agents Med Chem 21(9):1069–1081

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

We would like to express our gratitude to personnel of medical genetic lab at dep. of Medical Genetics.

Funding

This study was supported by Molecular Medicine Research Center (Grant No. 64694) of Tabriz University of Medical Sciences, Tabriz, Iran.

Author information

Affiliations

Authors

Contributions

ZT designed the study. MRA and ZT wrote the first draft of the manuscript. MP revised the manuscript for important intellectual content. SH, YR and DR contributed in gathering the data. MP and MRA supervised the study. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Majid Pornour or Mohammad Reza Alivand.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran with Ethics code IR.TBZMED.VCR.REC.1398.466.

Consent for publication

Not applicable.

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

Verify currency and authenticity via CrossMark

Cite this article

Torki, Z., Ghavi, D., Hashemi, S. et al. The related miRNAs involved in doxorubicin resistance or sensitivity of various cancers: an update. Cancer Chemother Pharmacol 88, 771–793 (2021). https://doi.org/10.1007/s00280-021-04337-8

Download citation

Keywords

  • microRNA
  • Doxorubicin
  • Cancer
  • Drug resistance
  • Chemosensitization
  • Combination therapy