Abstract Transmembrane protein TMEM119 has been implicated in tumor progression (e.g., ovarian cancer), but its role and underlying mechanism in ovarian endometriosis (EM) remain elusive. Thus, this study aimed to investigate the expression pattern and functional role of TMEM119 in ovarian EM. To this end, TMEM119 expression was first analyzed using the GSE141549 dataset, and further detected in ovarian EM tissues and ovarian ectopic endometrial stromal cells (ESCs). After TMEM119 overexpression in ectopic ESCs, GO/KEGG enrichment analyses of differentially expressed genes (DEGs) were conducted. For ectopic ESCs with TMEM119 knockdown or overexpression (divided into four groups: NC-shRNA, TMEM119-shRNA, NC-OE, and TMEM119-OE), we detected cell cycle distribution, positive rates of p16, p21, and p53, SA-β-GAL positivity, cell proliferation, and the expression of p53 and MAPK pathway-related proteins. Molecular docking was performed to evaluate the binding affinity between TMEM119 and therapeutic drugs for ovarian EM. Results showed that TMEM119 was significantly upregulated in ovarian EM tissues and ovarian ectopic ESCs. TMEM119 knockdown induced senescence in ectopic ESCs—evidenced by increased positive rates of p16 and p21, G0/G1 phase arrest, and accumulated SA-β-GAL positivity—accompanied by decreased cell proliferation and MAPK phosphorylation. In contrast, TMEM119 overexpression exerted the opposite effects. However, the change in p53 protein expression was not obvious. Molecular docking showed that TMEM119 exhibited strong binding affinity for Danazol, Drospirenone, and Sufugolix. Collectively, TMEM119 is significantly upregulated in ovarian EM, where it blocks ectopic endometrial stromal cell senescence via MAPK signalling and consequently accelerates lesion expansion. Inducing cellular senescence may therefore constitute a tractable therapeutic avenue for ovarian EM.
Zhang et al. (2026) studied this question.