Liu Ting, Cai Jian, Cai Jing, Wang Zehua, Cai Liqiong
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2021 Feb 25;10:608393. doi: 10.3389/fonc.2020.608393. eCollection 2020.
Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. However, the underlying mechanism of maintaining high EZH2 expression remains elusive. Here we showed that microRNA(miRNA) inhibited EZH2 by binding to the 3'-UTR of EZH2 mRNA; conversely, EZH2 can inhibit miRNA expression. We confirmed that a feedback loop exists between EZH2 and miRNA that maintained EZH2 overexpression, thus promoting ovarian cancer proliferation and . We further explored that EZH2 inhibited miRNA expression through PRC2, as determined by CHIP (chromatin immunoprecipitation), and EZH2 decreased the expression of p21, p53, and RUNX3. These results suggest that EZH2 inhibits the expression of Et-miRNAs (EZH2-targeting miRNAs) through the H3K27me3 pathway, thus forming an EZH2-miRNA positive feedback loop that maintains the high expression of EZH2 and promotes the malignant proliferation of cancer cells by regulating the expression of cell proliferation-related proteins.
锌指增强子同源物2（EZH2）是一种组蛋白甲基转移酶，通过多梳抑制复合物2（PRC2）介导H3K27me3，在卵巢癌中过表达并促进恶性增殖。然而，维持EZH2高表达的潜在机制仍不清楚。在此，我们发现微小RNA（miRNA）通过与EZH2 mRNA的3'-UTR结合来抑制EZH2；相反，EZH2可以抑制miRNA的表达。我们证实EZH2与miRNA之间存在一个反馈环，该反馈环维持EZH2的过表达，从而促进卵巢癌增殖。我们进一步探究发现，通过染色质免疫沉淀（CHIP）测定，EZH2通过PRC2抑制miRNA表达，并且EZH2降低了p21、p53和RUNX3的表达。这些结果表明，EZH2通过H3K27me3途径抑制Et-miRNA（靶向EZH2的miRNA）的表达，从而形成一个EZH2-miRNA正反馈环，该反馈环维持EZH2的高表达，并通过调节细胞增殖相关蛋白的表达促进癌细胞的恶性增殖。
