Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers

The transcription factor KLF5 is highly expressed in basal-like breast cancer (BLBC). It promotes cell proliferation, survival, migration and stemness and serves as a potential therapeutic target. In this study, we first identified a super-enhancer (SE) located downstream of the KLF5 gene in BLBC. JQ-1, a BRD4-bromodomain inhibitor, inhibits the expression and activity of KLF5 in the HCC1806 and HCC1937 cell lines in time- and dose-dependent manners. A new BRD4 inhibitor, compound 870, is more potent than JQ-1 in terms of its ability to inhibit KLF5 and BLBC growth by inducing G1 phase cell cycle arrest. Additionally, a CDK7 inhibitor, THZ1, also inhibits KLF5 and BLBC growth. Our findings suggested that SE regulates KLF5 and that SE inhibitors could be an effective therapeutic strategy for treating BLBC. ChIP-seq performed in this study was designed to detect the signal of BRD4 and H3K27Ac around KLF5 gene