KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1.

Abstract

Endometriosis is increasingly affecting women worldwide and research is focusing on identifying key targets in its pathogenesis. Changes in succinylation genes regulate the function of this protein and further influence the development of the disease. However, the role of succinylation genes in endometriosis is not clear from current studies. The expression of succinylation genes was determined in ectopic endometrium (EC) and ectopic patients with uterine fibroids (EN) by real-time quantitative PCR (qRT-PCR) and Western blot. Cell Counting Kit-8, transwell assays, and flow cytometry were used to assess endometrial stromal cells (ESCs) proliferation, apoptosis, migration, and invasion. KAT2A and ENO1 association was detected by qRT-PCR, immunofluorescence, and CoIP. We found that gene and protein levels of KAT2A were significantly increased in the EC group compared to EN group tissues. KAT2A silencing inhibited cell proliferation, migration, and invasion and promoted apoptosis. Western blot results showed that the expression of ENO1 and its succinylation was significantly upregulated in ECSc after KAT2A overexpression. CoIP results showed that KAT2A is positively bound to ENO1. Immunofluorescence also showed co-localized expression of KAT2A with ENO1. Furthermore, ENO1 overexpression reversed the effects of KAT2A silencing on the malignant behavior of ESCs. In summary, we found that succinylation of ENO1 mediated by KAT2A played a role in promoting the progression of endometriosis.