miR-490-3p modulates cell growth and epithelial to mesenchymal transition of hepatocellular carcinoma cells by targeting endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3)

J Biol Chem. 2013 Feb 8;288(6):4035-47. doi: 10.1074/jbc.M112.410506. Epub 2012 Dec 4.

Abstract

MicroRNAs (miRNAs) are considered to be regulators of various biological processes in cancers, including the epithelial to mesenchymal transition (EMT), which is a key factor in cancer metastasis. In this study, we aimed to clarify the potential roles of miR-490-3p in hepatocellular carcinoma (HCC) cells. Using real-time quantitative RT-PCR, we discovered that miR-490-3p was up-regulated in HCC tissues and cells compared with the adjacent non-tumor tissues and normal cells. We also found that overexpression of miR-490-3p led to an increase in cell proliferation, migration, and invasion abilities and that it contributed to EMT. The inhibition of miR-490-3p had the opposite effect on the cells. We identified ERGIC3 (endoplasmic reticulum-Golgi intermediate compartment protein 3) as a direct target gene for miR-490-3p. Unlike most miRNA-mRNA interactions, miR-490-3p increased ERGIC3 mRNA and protein levels as well as the intensity of expression of the EGFP reporter gene controlled by the 3'-UTR of ERGIC3 mRNA. The up-regulation by miR-490-3p also required the participation of Ago2. The inhibition of miR-490-3p reduced the expression of ERGIC3. Overexpression of ERGIC3 led to the same effect on HCC cells as miR-490-3p overexpression, including EMT. Importantly, silencing ERGIC3 reversed the cellular responses mediated by miR-490-3p overexpression. In conclusion, our study indicated for the first time that miR-490-3p functioned like an oncogenic miRNA in HCC cells and that the inhibition of miR-490-3p might provide an potential treatment approach for HCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Up-Regulation / genetics

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • ERGIC3 protein, human
  • MIRN490 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm