MiR-512-3p regulates malignant tumor behavior and multi-drug resistance in breast cancer cells via targeting Livin.

Breast cancer (BCa) is one of the most lethal malignancies of female reproductive organs. Increasing evidence has revealed that miRNAs participate in both tumorigenesis and multi-drug resistance. MiR-512-3p, a small non-coding RNA (miRNA), was previously found to be upregulated in breast cancer cells. In this study, we first verified that miR-512-3p expression forced a significant reorganization of the tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion and cell motility. Accordingly, induction of miR-512-3p expression significantly enhanced chemosensitivity and decreased metastatic potential in BCa cells. Our study demonstrated that miR-512-3p directly targets the 3'UTR of Livin, thereby decreasing its expression in MCF-7 cells. MiR-512-3p overexpression significantly inhibited breast cancer cell growth and metastasis. Both miR-512-3p overexpression and Livin knockdown significantly increased the chemosensitivity of cancer cells. Epirubicin (EPB), gemcitabine (GCB) and docetaxel (TXT) had antitumor effects in vitro against human breast cancer cell lines, and miR-512-3p overexpression increased tumor sensitivity to these drugs. In addition, miR-512-3p overexpression significantly inhibited tumor growth in vivo. Collectively, our data suggest that miR-512-3p is a significant regulator of tumorigenesis and drug resistance in breast cancer and provides evidence that miR-512-3p may represent a promising target for breast cancer therapy.