BRG1 promotes hepatocarcinogenesis by regulating proliferation and invasiveness

PLoS One. 2017 Jul 12;12(7):e0180225. doi: 10.1371/journal.pone.0180225. eCollection 2017.

Abstract

The chromatin remodeler complex SWI/SNF plays an important role in physiological and pathological processes. Brahma related gene 1(BRG1), a catalytic subunit of the SWI/SNF complex, is known to be mutated in hepatocellular carcinoma (HCC). However, its role in HCC remains unclear. Here, we investigate the role of BRG1 on cell growth and invasiveness as well as its effect on the expression of putative target genes. Expression of BRG1 was examined in human liver tissue samples and in HCC cell lines. In addition, BRG1 was silenced in human HCC cell lines to analyse cell growth and invasiveness by growth curves, colony formation assay, invasion assay and the expression of putative target genes. BRG1 was found to be significantly increased in HCC samples compared to non-HCC samples. In addition, a declined proliferation rate of BRG1-silenced human HCC cell lines was associated with a decrease of expression of cyclin family members. In line with a decreased invasiveness of BRG1-siRNA-treated human HCC cell lines, down-regulation of MMP7 was detected. These results support the hypothesis that overexpression of BRG1 increases cell growth and invasiveness in HCC. Furthermore, the data highlight cyclin B, E and MMP7 to be associated with BRG1 during hepatocarcinogenesis.

MeSH terms

  • Carcinogenesis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation*
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver / embryology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Up-Regulation

Substances

  • Cyclins
  • Nuclear Proteins
  • Transcription Factors
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • SMARCA4 protein, human
  • DNA Helicases

Grants and funding

This work was supported by the Wilhelm Sander-Stiftung (to D.H. and G.v.F.). Work in GVF's laboratory was supported by funding from the Deutsche Forschungsgemeinschaft (Emmy Noether Program, FI1719/2-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.