MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma

Gene. 2018 Jun 15:659:22-28. doi: 10.1016/j.gene.2018.03.053. Epub 2018 Mar 17.

Abstract

Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and shows rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Regulators of G-protein signaling (RGS) are critical for defining G-protein-dependent signal fidelity. RGS17 plays an important role in the regulation of cancer cell proliferation, migration and invasion. Here, we showed that miR-199 was downregulated in a hepatocarcinoma cell line. Overexpression of miR-199 significantly suppressed HCC cell proliferation, migration, and invasion in vitro. RGS17 overexpression promoted HCC cell proliferation, migration, and invasion, and reversed the miR-199 mediated inhibition of proliferation, migration, and invasion. Dual-fluorescence reporter experiments confirmed that miR-199 downregulated RGS17 by direct interaction with the 3'-UTR of RGS17 mRNA. In vivo studies showed that miR-199 overexpression significantly inhibited the growth of tumors. Taken together, the results suggested that miR-199 inhibited tumor growth and metastasis by targeting RGS17.

Keywords: Hepatocellular carcinoma; Migration; Proliferation; RGS17; miR-199.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RGS Proteins / genetics*

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RGS Proteins
  • RGS17 protein, human
  • mirn199 microRNA, human