RPA3 regulates NSCLC malignant phenotypes through epistatic functional association between GPR87 and p53.

This study aimed to clarify the functional regulatory links among RPA3, GPR87 and p53 in the tumorigenesis and progression of non-small cell lung cancer (NSCLC). Bioinformatic analysis and Western blot assays were performed to evaluate the expression profiles of RPA3 and GPR87 in NSCLC. CCK-8, EdU, wound healing, Transwell and flow cytometry assays were used to explore the effects of RPA3 knockdown on NSCLC proliferation, migration, invasion, cell cycle and apoptosis. Both pharmacological inhibition and siRNA-mediated knockdown of p53, together with GPR87 overexpression, were applied for in vitro and in vivo functional rescue verification. The results showed that RPA3 and GPR87 were highly expressed in NSCLC tissues and cells. RPA3 silencing inhibited cell proliferation, induced apoptosis and caused S-phase arrest in A549 and H23 cells. Notably, both GPR87 overexpression and genetic/chemical inhibition of p53 effectively rescued the tumor-suppressive phenotypes induced by RPA3 depletion. Cellular and xenograft experiments consistently confirmed that RPA3 modulates NSCLC malignant behaviors through functional phenotypic linkage of GPR87 and p53. In summary, RPA3 exerts oncogenic effects by regulating GPR87 and p53-dependent cellular functions, thereby promoting NSCLC cell proliferation, suppressing apoptosis and facilitating tumor growth.