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

International Journal of Biological Sciences
Chuan-Huizi ChenCeshi Chen

Abstract

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 KLF5 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.

Citations

Oct 19, 2019·The Journal of Biological Chemistry·Yingying WuCeshi Chen
Dec 12, 2019·Frontiers in Oncology·Manqing Wu, Jun Shen
Aug 22, 2020·Cancer Management and Research·Soyeon BangHongwei Zhang
Jan 4, 2021·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Wen-Hui LiaoMing-Jin Xie
Apr 4, 2021·Cancer Science·Yao Luo, Ceshi Chen

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Methods Mentioned

BETA
immunoprecipitation
PCR
electrophoresis
flow cytometry
fluorescence microscopy
ChIP-seq
FRET
xenograft

Software Mentioned

GraphPad Prism
ImageQuant
FlowJo
SPSS

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