Open AccessSuppression of bromodomain-containing protein 4 by shRNA: A new approach for cancer treatment
Author(s) -
Kaya Turan,
Berke Kahraman,
Nurgeldi Bazarov,
Alperen S Toker,
A. R. Celik,
Sadık Çiğdem,
Esra Gündüz
Publication year - 2016
Publication title -
clinical and investigative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.391
H-Index - 47
eISSN - 1488-2353
pISSN - 0147-958X
DOI - 10.25011/cim.v39i6.27493
Subject(s) - bromodomain , small hairpin rna , medicine , cancer research , cancer , oncology , biology , biochemistry , epigenetics , apoptosis , gene , gene knockdown
PURPOSEMYC is a transcription factor coding gene that is believed to control 15% of the genes in the entire human genome. The central role of c-MYC in cancer pathogenesis makes it a major therapeutic target in field of anticancer agent development.METHODSWe targeted the acetyl-lysine binding modules or bromodomains, which are associated with c-MYC transcriptional activation.RESULTSSequence specific inhibition of BET bromodomains with small hairpin RNAs (shRNAs) resulted in cessation of cellular proliferation in different cancer cell lines. Unlike previous studies on inhibition of bromodomains with selective small-molecule inhibitors, our study revealed the significant role of BET bromodomains in solid tumours and also highlighted the ease of RNA interference (RNAi) methodology for inhibition of bromodomain translation.CONCLUSIONThe degree of influence of BET bromodomain inhibition on proliferation in five cancer cell lines established it as the major target in malignancies characterized by activation of c-MYC.
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