Suppression of bromodomain-containing protein 4 by shRNA: A new approach for cancer treatment

Turan Kaya, Berke Kahraman, Nurgeldi Bazarov, Alperen S Toker, Ayse Celik, Sadik Cigdem, Esra Gunduz


Purpose: MYC 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.

Methods: We targeted the acetyl-lysine binding modules or bromodomains, which are associated with c-MYC transcriptional activation.

Results: Sequence 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.

Conclusion: The 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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