Journal
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Volume 28, Issue 1, Pages 36-44Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0394632015572070
Keywords
bromodomain and extraterminal domain proteins; epigenetics; epithelial-mesenchymal transition; hepatocellular carcinoma; prognosis
Categories
Funding
- National Key Sci-Tech Project [2012ZX10002011-002]
- National Natural Science Foundation of China [81472840, 81071741, 81030038]
- Shanghai Municipal Natural Science Foundation [14ZR1405800]
- PhD Programs Foundation of the Ministry of Education of China [20110072120050]
- Open Fund of Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education [KLCCI2014-8]
- China Postdoctoral Science Foundation [2014M561410]
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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.
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