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MicroRNA-134 modulates resistance to doxorubicin in human breast cancer cells by downregulating ABCC1

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Abstract

Objectives

To investigate the role of microRNAs in doxorubicin resistance of breast cancer cells.

Results

MicroRNA-134 was down-regulated in doxorubicin-resistant and doxorubicin-sensitive breast cancer samples and MCF-7/ADR cell lines. After transfection of miR-134 mimics, an MTT assay confirmed that the MCF-7/ADR cell proliferation was inhibited. In the presence of doxorubicin, there was inhibition of cell proliferation. Transfection of miR-134 mimics induced MCF-7/ADR cell apoptosis. The expression of ABCC1 was significantly upregulated in doxorubicin-resistant or -sensitive breast cancer tissues and MCF-7/ADR cell lines. Over-expression of miR-134 decreased the expression of ABCC1 at the protein level.

Conclusion

MicroRNA-134 modulates resistance to doxorubicin in breast cancer cells by downregulating the expression of ABCC1 which is known to encode the multidrug resistance-associated protein 1.

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References

  • Alder H, Taccioli C, Chen H, Jiang Y, Smalley KJ, Fadda P, Ozer HG, Huebner K, Farber JL, Croce CM, Fong LY (2012) Dysregulation of miR-31 and miR-21 induced by zinc deficiency promotes esophageal cancer. Carcinogenesis 33:1736–1744

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ali SM, Harvey HA, Lipton A (2003) Metastatic breast cancer: overview of treatment. Clin Orthopaed Rel Res 415:S132–S137

    Article  Google Scholar 

  • Angelini A, Ciofani G, Baccante G, Di Febbo C, Carmine DI, Cuccurullo F, Porreca E (2007) Modulatory effects of heparin on cellular accumulation and cytotoxicity of doxorubicin in MRP1-overexpressing HL60/doxo cells. Anticancer Res 27:351–355

    CAS  PubMed  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  • Bartels CL, Tsongalis GJ (2009) MicroRNAs: novel biomarkers for human cancer. Clin Chem 55:623–631

    Article  CAS  PubMed  Google Scholar 

  • Bonhoure E, Pchejetski D, Aouali N, Morjani H, Levade T, Kohama T, Cuvillier O (2006) Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting sphingosine kinase-1. Leukemia 20:95–102

    Article  CAS  PubMed  Google Scholar 

  • Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258:1650–1654

    Article  CAS  PubMed  Google Scholar 

  • Deeley RG, Westlake C, Cole SP (2006) Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 86:849–899

    Article  CAS  PubMed  Google Scholar 

  • Faversani A, Vaira V, Moro GP, Tosi D, Lopergolo A, Schultz DC, Rivadeneira D, Altieri DC, Bosari S (2014) Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors. Breast Cancer Res 16:R55

    Article  PubMed Central  PubMed  Google Scholar 

  • Fedele P, Calvani N, Marino A, Orlando L, Schiavone P, Quaranta A, Cinieri S (2012) Targeted agents to reverse resistance to endocrine therapy in metastatic breast cancer: where are we now and where are we going? Crit Rev Oncol/Hematol 84:243–251

    Article  Google Scholar 

  • Fodale V, Pierobon M, Liotta L, Petricoin E (2011) Mechanism of cell adaptation: when and how do cancer cells develop chemoresistance? Cancer J 17:89–95

    Article  CAS  PubMed  Google Scholar 

  • Gamucci T, D’Ottavio AM, Magnolfi E, Barduagni M, Vaccaro A, Sperduti I, Moscetti L, Belli F, Meliffi L (2007) Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer. Br J Cancer 97:1040–1045

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Garofalo M, Romano G, Di Leva G et al (2012) EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med 18:74–82

    CAS  Google Scholar 

  • Guo B, Villeneuve DJ, Hembruff SL, Kirwan AF, Blais DE, Bonin M, Parissenti AM (2004) Cross-resistance studies of isogenic drug-resistant breast tumor cell lines support recent clinical evidence suggesting that sensitivity to paclitaxel may be strongly compromised by prior doxorubicin exposure. Breast Cancer Res Treat 85:31–51

    Article  CAS  PubMed  Google Scholar 

  • Guo L, Liu Y, Bai Y, Sun Y, Xiao F, Guo Y (2010) Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cDNA expression analysis. Eur J Cancer 46:1692–1702

    Article  CAS  PubMed  Google Scholar 

  • Iorio MV, Croce CM (2009) MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 27:5848–5856

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA: Cancer J Clin 61:69–90

    Google Scholar 

  • Leivonen SK, Sahlberg KK, Makela R, Due EU, Kallioniemi O, Borresen-Dale AL, Perala M (2014) High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Mol Oncol 8:93–104

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Yao L, Liu F, Hong J, Chen L, Zhang B, Zhang W (2014) Characterization of microRNA expression in serous ovarian carcinoma. Int J Mol Med 34:491–498

    PubMed  Google Scholar 

  • Liu M, Chen H (2010) The role of microRNAs in colorectal cancer. J Gen Genomics 37:347–358 (in Chinese)

    Article  CAS  Google Scholar 

  • Magnani L, Stoeck A, Zhang X, Lanczky A, Mirabella AC, Wang TL, Gyorffy B, Lupien M (2013) Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer. Proc Natl Acad Sci USA 110:E1490–E1499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marquette C, Nabell L (2012) Chemotherapy-resistant metastatic breast cancer. Curr Treat Opt Oncol 13:263–275

    Article  Google Scholar 

  • Meng S, Cao J, Wang L, Zhou Q, Li Y, Shen C, Zhang X, Wang C (2012) MicroRNA 107 partly inhibits endothelial progenitor cells differentiation via HIF-1beta. PLoS One 7:e40323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mohd Sharial MS, Crown J, Hennessy BT (2012) Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer. Ann Oncol 23:3007–3016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Niu CS, Yang Y, Cheng CD (2013) MiR-134 regulates the proliferation and invasion of glioblastoma cells by reducing Nanog expression. Int J Oncol 42:1533–1540

    PubMed Central  CAS  PubMed  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA: Cancer J Clin 65:5–29

    Google Scholar 

  • Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC (2003) Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 21:588–592

    Article  PubMed  Google Scholar 

  • Xie Y, Tobin LA, Camps J, Wangsa D, Yang J, Rao M, Witasp E, Awad KS, Yoo N, Ried T, Kwong KF (2013) MicroRNA-24 regulates XIAP to reduce the apoptosis threshold in cancer cells. Oncogene 32:2442–2451

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yamanaka S, Campbell NR, An F, Kuo SC, Potter JJ, Mezey E, Maitra A, Selaru FM (2012) Coordinated effects of microRNA-494 induce G(2)/M arrest in human cholangiocarcinoma. Cell Cycle 11:2729–2738

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yang Y, Wu J, Guan H, Cai J, Fang L, Li J, Li M (2012) MiR-136 promotes apoptosis of glioma cells by targeting AEG-1 and Bcl-2. FEBS Lett 586:3608–3612

    Article  CAS  PubMed  Google Scholar 

  • Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG, Yang JM (2008) Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol 76:582–588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Correspondence to Xuezhen Ma.

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Lu, L., Ju, F., Zhao, H. et al. MicroRNA-134 modulates resistance to doxorubicin in human breast cancer cells by downregulating ABCC1 . Biotechnol Lett 37, 2387–2394 (2015). https://doi.org/10.1007/s10529-015-1941-y

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  • DOI: https://doi.org/10.1007/s10529-015-1941-y

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