MiR-944 functions as a novel oncogene and regulates the chemoresistance in breast cancer

MircroRNAs are emerging as critical regulators in carcinogenesis and chemoresistance in multiple cancer types. In this study, we observed that the miR-944 level was upregulated in breast cancer patients' serum and tumor tissues, suggesting that miR-944 is a tumor promoter in breast cancer. To investigate the role of miR-944, we performed gain- and loss-of-function experiments in vitro. We then demonstrated that miR-944 promotes cell proliferation and tumor metastasis in breast cancer cell lines. Furthermore, we indicated that miR-944 is associated with cisplatin resistance by targeting BNIP3. Knockdown of the miR-944 by specific inhibitors significantly increased the cytotoxicity of cisplatin in cisplatin-resistant MCF-7 cells (MCF-7/R). Importantly, we found that the sensitization of miR-944 inhibitors to cisplatin cytotoxicity was abolished by BNIP3 siRNA which decreased the expression of BNIP3 gene. Finally, we demonstrated that miR-944 inhibitors promoted the loss of mitochondrial membrane potential (MMP) caused by cisplatin in MCF-7/R cells, resulting in the release of mitochondria-derived apoptogenic proteins into cytoplasm, and then, the caspase-3 was activated. In summary, our study showed that miR-944 functions as a novel oncogene and regulates the cisplatin resistance in breast cancer. The miR-944-BNIP3-MMP-caspase-3 pathway might be a novel target for the chemotherapy of breast cancer.