MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma

BMC Cancer. 2014 Aug 27:14:616. doi: 10.1186/1471-2407-14-616.

Abstract

Background: The aberrant expression of microRNAs has been demonstrated to play a crucial role in the initiation and progression of hepatocarcinoma. miR-1246 expression in High invasive ability cell line than significantly higher than that in low invasive ability cell line.

Methods: Transwell chambers (8-uM pore size; Costar) were used in the in vitro migration and invison anssay. Dual luciferase reporter gene construct and Dual luciferase reporter assay to identify the target of miR-1246. CADM1 expression was evaluated by immunohistochemistric staining. The clinical manifestations, treatments and survival were collected for statistical analysis.

Results: Inhibition of miR-1246 effectively reduced migration and invasion of hepatocellular carcinoma cell lines. Bioinformatics and luciferase reporter assay revealed that miR-1246 specifically targeted the 3'-UTR of Cell adhesion molecule 1 and regulated its expression. Down-regulation of CADM1 enhanced migration and invasion of HCC cell lines. Furthermore, in tumor tissues obtained from liver cancer patients, the expression of miR-1246 was negatively correlated with CADM1 and the high expression of miR-1246 combined with low expression of CADM1 might serve as a risk factor for stage1 liver cancer patients.

Conclusions: Our study showed that miR-1246, by down-regulation CADM1, enhances migration and invasion in HCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Risk Factors
  • Survival Analysis

Substances

  • 3' Untranslated Regions
  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • MIRN1246 microRNA, human
  • MicroRNAs