Downregulation of microRNA-15a-3p is correlated with clinical outcome and negatively regulates cancer proliferation and migration in human osteosarcoma

J Cell Biochem. 2018 Jan;119(1):1215-1222. doi: 10.1002/jcb.26294. Epub 2017 Sep 18.

Abstract

In this study, we investigated the expression, correlation to clinical outcomes and biological functions of microRNA-15a-3p (miR-15a-3p) in human osteosarcoma. MiR-15a-3p expressions in osteosarcoma cell lines and clinical tissues of osteosarcoma patients were measured by qPCR. Relevance of endogenous miR-15a-3p to osteosarcoma patients' clinicopathological factors or overall survival was statistically analyzed. In addition, the independence of miR-15a-3p predicting cancer patients' overall survival was analyzed by Cox regression method. Furthermore, in osteosarcoma cell lines, Saos-2 and HOS cells, miR-15a-3p was overexpressed through stable lentiviral transduction. The functional regulations of miR-15a-3p overexpression on cancer ell proliferation and migration were then analyzed. MiR-15a-3p was significantly downregulated in osteosarcoma cell lines and human osteosarcoma tumors. Downregulation of endogenous miR-15a-3p in osteosarcoma tumors was significantly associated with cancer patient's poor clinical outcomes and low survival rate. Also, endogenous miR-15a-3p was confirmed to be an independent biomarker for predicating cancer patients' survival. In Saos-2 and HOS cells, lentivirus-induced miR-15a-3p overexpression had significantly tumor suppressing functions, by inhibiting both proliferation and migration. Significant downregulation of miR-15a-3p in osteosarcoma may be an independent biomarker to predicting cancer patients' poor prognosis. Overexpression miR-15a-3p may be an efficient functional meaning to suppress osteosarcoma development.

Keywords: clinical outcome; miR-15a-3p; osteosarcoma; overall survival; proliferation.

MeSH terms

  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Prognosis
  • Survival Analysis

Substances

  • MIRN15 microRNA, human
  • MicroRNAs