miR-34c-3p inhibits cell proliferation, migration and invasion of hepatocellular carcinoma by targeting MARCKS

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12728-37. eCollection 2015.

Abstract

Recent studies have shown that microRNA-34c-3p (miR-34c-3p) is down-regulated in various types of cancers and involved in tumor growth, invasion and metastasis. However, the roles of miR-34c-3p in hepatocellular carcinoma (HCC) are poorly understood. In this study, the expression profile of miR-34c-3pin HCC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of miR-34c-3p expression and clinicopathological characteristics were analyzed. The biological role of MiR-34c-3pin cell proliferation, migration and invasion was examined. In addition, the targets of miR-34c-3p were identified. The results showed that miR-34c-3p expression was significantly down-regulated in HCC tissues and cell lines; low expression level of miR-34c-3p was correlated with vascular invasion and advanced TNM stage. In vitro functional assays showed that overexpression of miR-34c-3pin HepG2 and Huh7 cells significantly reduced cell proliferation, migration and invasion. Furthermore, target analysis and luciferase assay identified myristoylated alanine-rich protein kinase c substrate (MARCKS) as a specific target of miR-34c-3p. Knockdown of MARCKS in HepG2 cells reduced cell migration and invasion, but not cell proliferation. Taken together, our findings implicate the potential application of miR-34c-3p as a tumor suppressor in cancer therapy.

Keywords: MARCKS; MiR-34c-3p; hepatocellular carcinoma; tumor suppressor.

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Staging

Substances

  • Intracellular Signaling Peptides and Proteins
  • MARCKS protein, human
  • MIRN34 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Myristoylated Alanine-Rich C Kinase Substrate