Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicatedin cancer, which play crucial roles in diverse biological processes, such asdevelopment, differentiation, apoptosis, and proliferation. The aim of this study wasto investigate whether miR-30c mediated the resistance of breast cancer cells to thechemotherapeutic agent doxorubicin (ADR) by targeting tyrosine3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30cwas downregulated in the doxorubicin-resistant human breast cancer cell linesMCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 celllines, respectively. Furthermore, we observed that transfection of an miR-30c mimicsignificantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover,the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferasereporter assay, and further studies indicated that the mechanism for miR-30c on thesensitivity of breast cancer cells involved YWHAZ and its downstream p38mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings providedevidence that miR-30c was one of the important miRNAs in doxorubicin resistance byregulating YWHAZ in the breast cancer cell line MCF-7/ADR.