Essential roles of BRD4 in cancer: DNA damage, transcription regulation, and signal transduction

Abstract

During cancer progression, bromodomain and extra-terminal (BET) families regulate chromatin and recruit enzymes that are associated with chromatin regulation to control gene expression. The bromodomain-containing protein 4 (BRD4) plays an important role in DNA damage repair, nuclear factor kappa B (NFκB) signaling, interaction with c-Myc, and transcription regulation of genes essential in carcinogenesis, as well as links transcription at enhancers and genes to regulate enhancer transcription. The colocalization of BRD4 with enhancer and promoter-proximal gene regions enables the elongation activation at enhancer genes. The inactivation of BRD4 has been demonstrated to inhibit cancer development, corroborating BRD4 as a promising therapeutic target. In addition, small-molecule inhibitors targetting functional domains of BRD4 are under investigation for their potential therapeutic applications in cancer and other diseases. This review presents an overview of BRD4 function and its dysfunction in cancer progression, as well as discusses how the potential of BRD4 as a therapeutic target.