miR-19 promotes osteosarcoma progression by targeting SOCS6

Biochem Biophys Res Commun. 2018 Jan 1;495(1):1363-1369. doi: 10.1016/j.bbrc.2017.10.002. Epub 2017 Oct 3.

Abstract

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-19 in human osteosarcoma (OS) development. Here, we showed that miR-19 was frequently upregulated in OS tissues and cell lines. Moreover the expression of miR-19 was associated with TNM stage, metastasis, size and poor overall survival. Mechanistically, miR-19 dramatically suppressed OS growth in vitro and in vivo. Bioinformatics analyses predicted that SOCS6 is a potential target gene of miR-19 in OS, which was confirmed by luciferase-reporter assay. We also found that SOCS6 expression was downregulated and negatively correlated with miR-19 expression in OS tissues clinically. Moreover, ectopic SOCS6 could reverse miR-19 induced OS growth. Finally, JAK2/STAT3 signaling pathway involves miR-19/SOCS6-mediated OS progression. Together, our data provide important evidence for miR-19 mediated SOCS6 in OS growth and revealed miR-19/SOCS6/JAK2/STAT3 pathway as a potential therapeutic strategy for OS patients.

Keywords: Growth; JAK2/STAT3 pathway; Osteosarcoma; SOCS6; miR-19.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology*
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Up-Regulation

Substances

  • MIRN19 microRNA, human
  • MicroRNAs
  • SOCS6 protein, human
  • Suppressor of Cytokine Signaling Proteins