Int J Biol Sci 2019; 15(8):1733-1742. doi:10.7150/ijbs.35138
Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers
1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China
2. School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, China
3. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan, 410013, China
4. School of Pharmaceutical Science, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiang'an South Road, Xiamen, Fujian, 361102, China
5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beichen West Road, Chaoyang District, Beijing, 100101, China
6. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China, 510095.
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.
Keywords: KLF5, Super-enhancer, BRD4, JQ-1, THZ1, BLBC
Chen CH, Yang N, Zhang Y, Ding J, Zhang W, Liu R, Liu W, Chen C. Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. Int J Biol Sci 2019; 15(8):1733-1742. doi:10.7150/ijbs.35138. Available from http://www.ijbs.com/v15p1733.htm