{"paper_id":"b2dbeb0a-96b1-412c-9331-988fbdc52c3a","body_text":"Abstract\nBackground: Endometriosis (EMs) is a common benign gynecological disorder affecting women of reproductive age, characterized by ectopic endometrial growth, invasion, and periodic bleeding. Mounting evidence indicates that metabolic reprogramming, particularly hyperactive glycolysis, critically promotes the pathological progression of EMs. Phosphatase and tensin homolog (PTEN), a pivotal tumor suppressor and endometrial housekeeping gene, is frequently downregulated in EMs; however, its precise regulatory mechanism linking glycolysis and EMs pathogenesis remains largely unexplored.\nMethods: Bioinformatics analysis was applied to characterize PTEN expression and its correlation with glycolysis-associated genes in EMs. In vitro, PTEN was knocked down in human normal endometrial stromal cells (NESC) and overexpressed in human endometriotic epithelial cells (12Z), while both cell types were treated with the PTEN inhibitor SF1670, followed by phenotypic and glycolytic assessments. In vivo, an EMs mouse model was used to verify the effects of PTEN inhibition on ectopic lesion development and glycolytic metabolism by pathological and molecular detection.\nResults: PTEN expression was significantly downregulated in ectopic lesions compared with normal and eutopic counterparts, and exhibited an opposite expression trend to the core glycolytic regulators glucose transporter type 1 (Glut1) and pyruvate dehydrogenase kinase 1 (PDK1). In cellular experiments, endogenous PTEN protein levels were also markedly lower in 12Z cells than in NESC cells. Functional experiments demonstrated that loss of PTEN via knockdown or pharmacological inhibition with SF1670 markedly reinforced cell proliferation, migration, invasion, and glycolytic metabolism, whereas PTEN overexpression effectively alleviated these malignant biological behaviors. In line with in vitro observations, in vivo studies further demonstrated that SF1670-mediated PTEN inhibition significantly promoted ectopic lesion growth, primarily by suppressing PTEN expression, and this effect was accompanied by enhanced glycolytic activity in lesion tissues.\nConclusion: This study reveals that PTEN expression correlates with EMs progression and is inversely associated with glycolytic activity, suggesting a potential PTEN-glycolysis association that may serve as a target for diagnosis and therapy.\nKeywords\n- endometriosis\n- phosphatase and tensin homolog\n- glycolysis\n- lactate dehydrogenase\n- proliferation\n- migration\n- invasion","source_license":"CC0","license_restricted":false}