MicroRNA-181a Modulates Chemosensitivity Of Breast Cancer Cells To Adriamycin By Targeting Bcl-2

Objectives:miR-181a is involved in immunity, metabolism, tumor suppression or carcinogenesis reported by many other studies. However, its role in the development of chemosensitivity to adriamycin in low-invasive breast cancer cells remains unclear. The aim of this study is to define the function role of miR-181a in promoting the efficacy of adriamycin-based neoadjuvant chemotherapy.Methods:Real-time PCR was performed to test the expressions of miR-181a in MCF-7and MCF-7/ADR cells. Cells were transfected with miR-181a mimics or inhibitor using lipofectamine2000. By real-time fluorescence quantitative PCR and Western blot, we detected the expression of Bcl-2in two groups before and after transfection. Cell Counting Kit-8assay and apoptosis assay were performed to observe the impact of miR-181a expression on the sensitivity of breast cancer cells to ADR. Quantitative real-time PCR (qRT-PCR) detection was performed to study the expression level of miR-181a and Bcl-2and the correlation between them in selected breast cancer tissue samples with neoadjuvant chemotherapy. Statistical analysis:The results were treated by SPSS20.0software statistics. The experiment were repeated independently for at least three times, and got a good reproducibility. Data was show as mean±standard deviation, analysis of variance between groups used one-way ANOVA method. Correlation between groups was analyzed using Spearman rank test. p<0.05was considered statistically significant. Results:miR-181a significantly downregulated in the MCF-7/ADR compared with its parental MCF-7cell line. Transfected with miR-34a mimic in cells resulted in upregulated expression of Bcl-2mRNA and protein. On the contrary, the expression of Bcl-2mRNA and protein in MCF-7cells transfected with miR-181a inhibitor were down-regulated. The alteration of miR-181a expression did significantly affect the chemosensitivity to adriamycin in MCF-7and MCF-7/ADR cells. Further, a negative relationship between miR-181a and Bcl-2is observed in breast cancer. Compared with that in the responders group, miR-181a was dramatically reduced in the nonresponders group, with a positive correlation with ADR chemosensitivity. Instead, Bcl-2mRNA expression was increased in the nonresponders group, with a negative correlation with ADR chemosensitivity.Conclusions:At least in part, the detection of miR-181a may direct the clinical medication in patients with neoadjuvant chemotherapy because of miR-181a enhanced adriamycin-induced apoptosis via targeting Bcl-2.