Basement membrane-associated gene P3H2 regulates osteosarcoma progression and epithelial-mesenchymal transition through AKT/mTOR signaling axis.

BACKGROUND: Osteosarcoma is a primary malignant bone tumor that primarily affects adolescents and children, is highly metastatic and invasive, and has a poor survival prognosis. P3H2 is a basement membrane-associated tumor suppressor gene that is down-regulated in some types of tumors. Although some studies have shown that P3H2 has a tumor suppressive effect in some cancers, its role and specific mechanism in osteosarcoma remain unclear. Further analysis of the function and mechanism of the basement membrane-related gene P3H2 in osteosarcoma is expected to provide new insights for early diagnosis and treatment, prognosis evaluation, and targeted drug development. METHODS: In this study, we first investigated the dysregulation of P3H2 in osteosarcoma and pan-cancer by using public databases and bioinformatics analysis. Further, we confirmed the expression of P3H2 in osteosarcoma cell lines. Subsequently, we investigated the effect of P3H2 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells through in vitro and in vivo experiments. Finally, we investigated the mechanism by which P3H2 affects the malignant behavior of osteosarcoma through a response experiment. RESULTS: Through comprehensive bioinformatic analysis, this study revealed the expression, prognostic value, and immunomodulatory role of P3H2 in a variety of tumors. Subsequent experiments showed that P3H2 could inhibit the proliferation, migration, invasion, and EMT of osteosarcoma cells, and inhibit the growth of subcutaneous tumors. Mechanistically, P3H2 inactivates AKT/mTOR signaling by inhibiting AKT and mTOR phosphorylation, thereby inhibiting proliferation, migration, invasion, and EMT of osteosarcoma cells. CONCLUSION: As a tumor suppressor gene in osteosarcoma, P3H2 inhibits the malignant biological behavior of osteosarcoma by inhibiting the AKT/mTOR signaling axis.