EZH2 regulates expression of FOXC1 by mediating H3K27me3 in breast cancers

• 作者: Xiang-jin Zheng Wan Li Jie Yi Jin-yi Liu Li-wen Ren Xiao-ming Zhu Shi-wei Liu Jin-hua Wang Guan-hua Du
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（7）
• 所属期刊栏目: Anti-tumor Pharmacology
• 页码范围: 1171-1179
• 页数: 9页
• 语种: 英文

摘要

Triple-negative breast cancer(TNBC)is characterized by low expression of human epidermal growth factor receptor-2(HER2),estrogen receptor(ER),and progesterone receptor(PR),which is the most aggressive subtype with poor outcome among breast cancers.The underlying mechanisms of TNBC remain unclear and there is a lack of biomarkers.In this study we conducted an in silico assay and found that FOXC1 was highly expressed in ER-/PR-/HER2-breast cancers,which was confirmed by qRT-PCR,immunohistochemistry,and Western blot analysis.FOXC1 was more highly expressed in TNBCs than the other breast cancers.Kaplan-Meier plotter revealed that expression of FOXC1 was associated with overall survival(OS)of patients with breast cancers.Expression of FOXC1 was reversely associated with level of H3K27me3,which was methylated by EZH2.In MCF-7 and T47D cells,inhibition of EZH2 by DZNeP or GSK343 concentration-and time-dependently increased expression of FOXC1.Finally,we demonstrated that the expression of FOXC1 was associated with resistance of doxorubicin treatment of breast cancer cells.In conclusion,these results suggest that FOXC1 may be a potential biomarker or drug target for TNBCs,and that downregulation of FOXC1 could have therapeutic value in treatment of TNBCs.