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

Abstract

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly 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 luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

Novel prognostic and predictive microRNA targets for triple‐negative breast cancer

“…Lower expression levels of miR-30c were noted in triplenegative cell lines and basal tumors, further confirming its tumor-suppressive role in TNBC (63,64). A recent study found that miR-30c-5p was downregulated in doxorubicin-resistant breast cancer cell lines, whereas overexpression of miR-30c-5p inhibited the anti-apoptotic gene tyrosine 3-monooxygenase/ tryptophan 5-monooxygenase activation protein zeta (YWHAZ) and resensitized tumor cells to doxorubicin treatment (65). This supports a key role of miR-30c in drug sensitivity, as well as the potential of monitoring miRNA expression profiles throughout treatment course as an indicator for patient resistance to therapy.…”

Key microRNAs in the biology of breast cancer; emerging evidence in the last decade

“…miR-125b targets the repression of Bak1 impacts the resistance to paclitaxel, and fluorouracil, epirubicin, and cyclophosphamide in both breast tumor samples and BC cell lines (Climent et al, 2007;. In other studies, miR-30c showed its sensitizing impact on taxol, paclitaxel, and doxorubicin response (Bockhorn et al, 2013;Fang et al, 2014).…”

Computational analysis of 3′UTR region of CASP3 with respect to miRSNPs and SNPs in targetting miRNAs

“…In addition, detailed researches showed that the mechanism for miR-30c-5p, the experimentally verified target of the anti-apoptotic gene YWHAZ, on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway (Fang et al, 2014). Furthermore, the expression of miR-30c-5p is notably increased in sulfuretin-stimulated cells, hereby inducing cell cycle arrest and apoptosis in human cancer cell lines (Poudel et al, 2013).…”