Histone demethylase KDM7A is required for stem cell maintenance and apoptosis inhibition in breast cancer

组蛋白去甲基化酶 KDM7A 是乳腺癌干细胞维持和细胞凋亡抑制所必需的

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作者:Zhenzhen Meng, Ying Liu, Jie Wang, Hongjia Fan, Huan Fang, Sha Li, Lin Yuan, Cuicui Liu, You Peng, Weiwei Zhao, Lulu Wang, Jing Li, Jing Feng

Abstract

Histone demethylase KDM7A regulates neuronal differentiation and development in mammals. In this study, we found that KDM7A was also required for breast cancer stem cells (BCSCs) maintenance. Silencing KDM7A significantly reduced the BCSCs population and mamosphere formation in vitro, and inhibited breast tumor growth in vivo. Restoring KDM7A expression rescued the defect in stem cell maintenance. Our mechanism analysis suggested that KDM7A upregulated the stemness-associated factors KLF4 and c-MYC for BCSCs maintenance. In addition, KDM7A knockdown promoted apoptosis through decreasing BCL2 expression and BAD phosphorylation in breast cancer (BrCa). Furthermore, restoring KDM7A and BCL2 expression rescued apoptosis inhibition in breast cancer, suggesting that KDM7A inhibited apoptosis by upregulating the BCL2 level in breast cancer. In conclusion, KDM7A promotes cancer stem cell maintenance and apoptosis inhibition in breast cancer.

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