MicroRNA-127-3p acts as a tumor suppressor in epithelial ovarian cancer by regulating the BAG5 gene

Oncol Rep. 2016 Nov;36(5):2563-2570. doi: 10.3892/or.2016.5055. Epub 2016 Aug 29.

Abstract

In the present study, the tumor-suppressive role of microRNA-127-3p (miR-127-3p) in epithelial ovarian cancer (EOC) was elucidated. Expression of miR-127-3p was examined by quantitative RT-PCR (qRT-PCR) in 9 EOC cell lines and clinical samples from 13 EOC patients. EOC cell lines, OVCAR-3 and Caov-3, were transduced with a lentivirus to overexpress endogenous miR-127-3p. The tumor-suppressive effects of miR-127-3p on EOC proliferation, bufalin sensitivity, invasion and in vivo growth were investigated through proliferation, bufalin sensitivity wound-closure and in vivo tumorigenicity assays, respectively. In addition, luciferase reporter assay and qRT-PCR were conducted to verify whether the Bcl-2-associated athanogene 5 (BAG5) gene was the downstream target of miR-127-3p in EOC. BAG5 was subsequently upregulated in the OVCAR-3 and Caov-3 cells to examine its functional correlation with miR‑127-3p regulation in EOC. The results revealed that in both EOC cell lines and EOC tumor tissues, miR-127-3p was downregulated. Lentiviral-mediated miR-127-3p overexpression exerted tumor-suppressive effects in OVCAR-3 and Caov-3 cells by reducing in vitro proliferation and invasion, increasing bufalin sensitivity, and inhibiting in vivo tumor growth. miR‑127-3p directly regulated the BAG5 gene in EOC. Subsequent BAG5 upregulation ameliorated the tumor-suppressive effects of miR-127-3p overexpression in EOC. In conclusion, miR-127-3p functions as a tumor suppressor in EOC, and its influence on EOC is directly through regulation of BAG5.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adaptor Proteins, Signal Transducing / biosynthesis*
  • Adaptor Proteins, Signal Transducing / genetics
  • Apoptosis / genetics
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Lentivirus / genetics
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • BAG5 protein, human
  • MIRN127 microRNA, human
  • MicroRNAs