PPM1D accelerates proliferation and metastasis of osteosarcoma by activating PKP2.

Objective This project aims to elucidate the diagnostic and prognostic values of PPM1D in osteosarcoma and the molecular mechanism. Patients and methods PPM1D levels in osteosarcoma and adjacent tissues were detected. Pathological information of included osteosarcoma patients was collected for analyzing the relationship between PPM1D and prognosis of osteosarcoma. Regulatory effects of PPM1D on in vivo and in vitro progressions of osteosarcoma were assessed by generating xenograft model in nude mice and PPM1D knockdown models in MG63 and U2OS cells, respectively. The involvement of PKP2, the target gene of PPM1D in osteosarcoma progression was finally evaluated. Results PPM1D was upregulated in osteosarcoma tissues than adjacent ones. High level of PPM1D indicated higher risks of distant metastasis and worse prognosis in osteosarcoma. In vivo knockdown of PPM1D contributed to a delay in tumor growth of osteosarcoma in nude mice. PKP2, as the downstream gene targeting PPM1D, was highly expressed in osteosarcoma tissues and positively correlated to PPM1D level. The overexpression of PKP2 was able to abolish the inhibited proliferative and migratory abilities in osteosarcoma cells with PPM1D knockdown. Conclusions PPM1D triggers proliferative and migratory abilities of osteosarcoma by positively regulating PKP2, which can be served as an effective diagnostic marker for osteosarcoma in the early phase.