PSG11 Overexpression Promotes Epithelial Ovarian Cancer Progression via Hedgehog-Mediated Autophagy Regulation
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Background: Epithelial ovarian cancer (EOC) is a highly lethal gynecologic malignancy due to late diagnosis, frequent recurrence, and a lack of effective early biomarkers. This study investigates the role of pregnancy-specific glycoprotein 11 (PSG11) in EOC progression and its potential as a therapeutic target. Methods: PSG11 expression and its prognostic significance in epithelial ovarian cancer were analyzed using The Cancer Genome Atlas data and Gene Expression Omnibus, validated by immunohistochemistry. PSG11 expression in epithelial ovarian cancer cell lines was confirmed via Quantitative Polymerase Chain Reaction and Western blot. PSG11 knockdown was studied using flow cytometry,celigo counting,cloning experiment, scratch assay,transwell assays and tumor models in nude mice, with bioinformatics analyses providing insights into the mechanisms involved. Results: PSG11 was significantly overexpressed in EOC tissues compared to para-cancerous tissues (47.2% vs. 12.5%, P < 0.001). A significant correlation was observed between high PSG11 expression and FIGO stage, distant metastasis, tumor size, and lymph node involvement ( P < 0.001, P = 0.004, P = 0.017, and P = 0.019, respectively). Functional studies demonstrated that PSG11 knockdown reduced cell viability by approximately 40% ( P < 0.001), colony formation by approximately 50%, and migration rates by approximately 60% in vitro, while promoting apoptosis. In vivo, PSG11 knockdown suppressed tumor growth, reducing tumor volume by approximately 55% and tumor weight by approximately 50% by day 30. Mechanistically, PSG11 activated the Hedgehog signaling pathway, promoting epithelial ovarian cancer progression by regulating autophagy. Conclusion: PSG11 drives epithelial ovarian cancer progression by activating Hedgehog signaling to regulate autophagy. These findings identify PSG11 as a potential therapeutic target in EOC.