BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma

Int J Immunopathol Pharmacol. 2015 Mar;28(1):36-44. doi: 10.1177/0394632015572070.

Abstract

Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that play an important role in chromatin remodeling and transcriptional regulation. In this study, we found that BRD4, a BET family member, is significantly upregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues. Furthermore, the overexpression of BRD4 in cancer tissues was correlated with poor prognosis in HCC patients. Using shRNA-mediated knockdown of BRD4 or lentivirus-mediated overexpression of BRD4 in HCC cells, we further showed that BRD4 was involved in HCC cell growth and invasion in vitro. Forced expression of BRD4 was sufficient to induce epithelial-mesenchymal transition (EMT) phenotypes in HCC cells. Additionally, BRD4 shRNA significantly inhibited HCC cell proliferation in vivo. Collectively, our study confirmed that BRD4 expression is a valuable predictor of recurrence and survival in patients with HCC. BRD4 can be further used as a potential therapeutic target of HCC.

Keywords: bromodomain and extraterminal domain proteins; epigenetics; epithelial-mesenchymal transition; hepatocellular carcinoma; prognosis.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Nuclear Proteins / genetics*
  • RNA, Small Interfering / genetics
  • Transcription Factors / genetics*
  • Transcriptional Activation / genetics
  • Up-Regulation / genetics

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Transcription Factors