POLQ promotes tumor progression and immunosuppression via ATM‑P53 signaling in endometrial cancer

Endometrial cancer (EC) is a one of the most prevalent gynecological malignancies worldwide; however, the molecular mechanisms driving its progression remain insufficiently understood. In the present study, DNA polymerase θ (POLQ), which is implicated in multiple types of cancer, was comprehensively investigated in EC using data from The Cancer Genome Atlas and TNMplot datasets, with further validation in an independent patient cohort. POLQ expression was markedly upregulated in EC tissues and was associated with reduced 15‑year overall survival. Increased POLQ levels were also associated with higher Ki67 proliferation indices, distinct patterns of T‑cell infiltration and enhanced programmed death‑ligand 1 (PD‑L1) expression. Gene Set Enrichment Analysis revealed that POLQ expression was associated with pathways involved in cell proliferation, cell cycle regulation and DNA damage repair. Mechanistic studies based on POLQ knockdown in EC cells were conducted <i>in vitro</i> using small interfering RNA‑mediated gene silencing, followed by functional assays including cell proliferation assay, flow cytometric cell cycle analysis, apoptosis assay, migration and invasion assays, and western blot analysis to detect the expression of key proteins involved in ATM/P53 signaling and epithelial‑mesenchymal transition (EMT) regulation. These experiments further demonstrated that POLQ may accelerate EC progression via two complementary mechanisms: i) Activation of ataxia‑telangiectasia mutated/P53 signaling to facilitate cell cycle checkpoint bypass; and ii) induction of EMT via cadherin switching. Collectively, these findings established POLQ as a robust prognostic biomarker and a promising therapeutic target in EC.