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Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers
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Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers
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Journal Article
Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers
2019
Overview
The transcription factor KLF5 (Krüpple-like factor 5) is highly expressed in basal-like breast cancer (BLBC), which promotes cell proliferation, survival, migration and stemness, serving as a potential therapeutic target. In the current study, a super-enhancer (SE) was identified to be located downstream of the
gene in BLBC cell lines, HCC1806 and HCC1937. JQ-1, a BRD4 inhibitor, inhibits the expression and activity of KLF5 in both HCC1806 and HCC1937 cells in a time- and dose-dependent manner. Compound 870, an in-house BRD4 inhibitor, exhibited higher potency than JQ-1 to inhibit KLF5 and BLBC growth by arresting cells in G1 phase. Additionally, THZ1, a CDK7 inhibitor, also inhibits KLF5 and BLBC growth in a similar manner. Our findings suggested that KLF5 is regulated by SE, and modulation of SE could be an effective therapeutic strategy for treating BLBC.
Publisher
Ivyspring International Publisher Pty Ltd,Ivyspring International Publisher
Subject
/ Cell Proliferation - drug effects
/ Cell Proliferation - genetics
/ Chromatin Immunoprecipitation
/ G1 phase
/ G1 Phase Cell Cycle Checkpoints - drug effects
/ G1 Phase Cell Cycle Checkpoints - genetics
/ Humans
/ Kruppel-Like Transcription Factors - genetics
/ Kruppel-Like Transcription Factors - metabolism
