RND3 Inhibits Endometriosis Progression by Regulating Autophagy and Oxidative Stress Through PLEKHG5

Endometriosis (EMS) is a chronic gynecological disease. RND3 is recognized as a potential autophagy-related biomarker in EMS. The aim of this study was to investigate the regulatory role of RND3 on autophagy and oxidative stress in EMS. Immunohistochemistry (IHC), RT-qPCR, and western blot (WB) analyses were used to determine the expression levels of RND3 and PLEKHG5. The study assessed oxidative stress by examining NRF2/NQO-1/HO-1 expression, as well as GSH, SOD, MDA levels, and lipid ROS production. Autophagy was evaluated by analyzing the expression of autophagy-related markers and phosphorylation of PI3K, AKT, ERK1/2, and mTOR. Cell proliferation, migration, and invasion were evaluated using CCK-8 and Transwell assays. Apoptosis was assessed through flow cytometry, expression of apoptosis-related markers, and TUNEL assay. The study also used ELISA to measure inflammatory factor levels and Co-IP assay to investigate the interaction between RND3 and PLEKHG5. Low expression of RND3 was observed in both the eutopic and ectopic endometrial tissues and ectopic endometrial stromal cells (EESCs) from patients with EMS. Increasing RND3 levels reduced oxidative stress in EESCs, enhanced cellular autophagy, inhibited cell proliferation, migration, and invasion, and promoted apoptosis. Conversely, the knockdown of RND3 expression had the opposite effect. The impact of RND3 overexpression on oxidative stress, autophagy, and apoptosis in EESCs was reversed by si-NRF2 and the autophagy inhibitor CQ. RND3 overexpression also upregulated the expression of PLEKHG5 in EESCs. Co-IP results revealed an interaction between RND3 and PLEKHG5. In in vivo experiments, low PLEKHG5 expression was observed in endometrial tissues of EMS mice, while RND3 overexpression alleviated EMS symptoms by decreasing oxidative stress and promoting cellular autophagy and apoptosis. RND3 inhibits EMS progression by enhancing autophagy and suppressing oxidative stress through PLEKHG5.