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

Tumour Biol. 2016 Feb;37(2):1599-607. doi: 10.1007/s13277-015-3844-x. Epub 2015 Aug 23.


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.

Keywords: BNIP3; Breast cancer; Cisplatin resistance; MiR-944; Oncogene.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / genetics
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oncogenes
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Real-Time Polymerase Chain Reaction
  • Transfection
  • Up-Regulation


  • Antineoplastic Agents
  • BNIP3 protein, human
  • MIRN-944 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Cisplatin