MicroRNA-4262 activates the NF-κB and enhances the proliferation of hepatocellular carcinoma cells

Int J Biol Macromol. 2016 May:86:43-9. doi: 10.1016/j.ijbiomac.2016.01.019. Epub 2016 Jan 8.

Abstract

microRNAs (miRNAs) were known as transcriptional regulators to regulate the repertoires of target genes during the development of hepatocellular carcinoma (HCC). In this study, we investigated the roles of miR-4262 in the process of HCC. Our results showed that miR-4262 is overexpressed in HCC tissues and hepatoma cell lines (HepG2 and Sk-hep-1). We also found that miR-4262 enhanced the process of cell cycle and inhibited the apoptosis leading to promoted cell proliferation and activity. Moreover, the 3'UTR of PDCD4 was complementary to miR-4262 seed region and we confirmed that PDCD4 is the direct target of miR-4262 with 3'UTR luciferase assay. qPCR and WB analysis revealed that the level of PDCD4 was negatively correlated with the expression of miR-4262 in HepG2 cells. Furthermore, our results demonstrated that miR-4262-promoted cell proliferation was mediated by PDCD4 and miR-4262 can activate the NF-κB pathway to promote the accumulation of nuclear NF-κB/P65. All of these findings suggested miR-4262 may play a role in the development of HCC.

Keywords: Hepatocellular carcinoma; PDCD4; miR-4262.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / genetics
  • Cell Proliferation / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Signal Transduction / genetics
  • Transcription Factor RelA / metabolism*
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • Transcription Factor RelA
  • microRNA-4262 microRNA, human