MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma

Cell Physiol Biochem. 2016;38(2):777-85. doi: 10.1159/000443033. Epub 2016 Feb 15.

Abstract

Background/aims: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC).

Methods: Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo.

Results: miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice.

Conclusion: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver / metabolism
  • Liver / pathology*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic
  • Receptors, CXCR6
  • Receptors, Chemokine / genetics*
  • Receptors, Virus / genetics*

Substances

  • CXCR6 protein, human
  • MIRN361 microRNA, human
  • MicroRNAs
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Virus