NAT10 mediated polycystic ovary syndrome through the ac4C modification of CXCL14.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age, underscoring the critical importance of investigating its regulatory mechanisms. N-Acetyltransferase 10 (NAT10) is a crucial enzyme involved in mRNA acetylation modification, mediating target genes expression through N4-acetylcytidine (ac4C) modification to regulate the biological function of various diseases. Nonetheless, the specific role of NAT10 in PCOS regulation remains undisclosed. Ac4C dot hybridization experiment was conducted to determine ac4C expression in PCOS tissues. RT-qPCR was employed to assess the expression levels of NAT10 and CXCL14 in PCOS tissues and KGN cells. Cells viability was assessed using the CCK-8 method, while cell proliferation capacity was evaluated through the colony formation assay and EDU assay. Flow cytometry analysis was utilized to measure the apoptosis rate. The ac4C modification level was determined by acrp-qPCR analysis. RIP and luciferase reporter experiments confirmed the target binding relationship. The rat experiments confirmed the specific regulatory role of NAT10 in polycystic ovary syndrome in vivo. This study highlighted reduced levels of NAT10 and ac4C in PCOS, where silencing NAT10 boosts KGN cell proliferation and suppresses apoptosis. Additionally, NAT10-mediated ac4C modification governed the chemokine CXCL14 expression. Our research unveiled that NAT10 modulated PCOS occurrence and progression by enhancing the CXCL14 mRNA stability through acetylation, presenting potential novel insights into the mechanisms of mRNA acetylation in PCOS.