miR-5195-3p Suppresses Cell Proliferation and Induces Apoptosis by Directly Targeting NEDD9 in Osteosarcoma

Cancer Biother Radiopharm. 2019 Aug;34(6):405-412. doi: 10.1089/cbr.2018.2761.

Abstract

Objective: Aberrantly expressed microRNAs (miRs) have associated with the development and progression of osteosarcoma (OS). In this study, the authors aimed to investigate the biological function of miR-5195-3p and the underlying mechanisms. Methods: Quantitative real-time polymerase chain reaction analysis was performed to determine the expression of miR-5195-3p in OS tissues and cell lines. Then, two OS cell lines (MG-63 and U2OS) were transfected with miR-5195-3p mimics to obtain stably miR-5195-3p overexpression cell lines. A series of functional assays, including Cell Counting Kit-8 assay, colony formation assay, flow cytometry assay, and Hoechst staining were performed to analyze cell proliferation and apoptosis. Results: The authors first observed downregulation of miR-5195-3p in OS tissues and cell lines. A series of functional assays demonstrated that miR-5195-3p overexpression significantly attenuated OS cell proliferative activity and induced apoptosis. At a molecular level, the neural precursor cell which expressed developmentally downregulated protein 9 (NEDD9), was inversely correlated with the expression level of miR-5195-3p. Furthermore, ectopic expression of NEDD9 counteracted the antiproliferative and apoptotic effects of miR-5195-3p overexpression in OS cells. Conclusions: In summary, the miR-5195-3p/NEDD9 axis may be a promising antitumor agent for OS.

Keywords: NEDD9; apoptosis; cell proliferation; miR-5195-3p; osteosarcoma.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MIRN5195 microRNA, human
  • MicroRNAs
  • NEDD9 protein, human