title: MiR-944 functions as a novel oncogene and regulates the chemoresistance in breast cancer.
abstract: 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.
authors: Department of Surgical Oncology, The Second Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
authors: Haifei
authors: H
authors: He
authors: Department of Surgical Oncology, The Second Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.|Cancer Institute (The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
authors: Wei
authors: W
authors: Tian
authors: Department of Surgical Oncology, The Second Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.|Cancer Institute (The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
authors: Hailong
authors: H
authors: Chen
authors: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Gucui Road 234#, Xihu District, Hangzhou city province, Zhejiang, 310012, China. wzjiangkai@163.com.
authors: Kai
authors: K
authors: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C090121:BNIP3 protein, human; C000603398:MIRN944 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D002945:Cisplatin
keywords: BNIP3; Breast cancer; Cisplatin resistance; MiR-944; Oncogene