MAT2B promotes proliferation and inhibits apoptosis in osteosarcoma by targeting epidermal growth factor receptor and proliferating cell nuclear antigen

Abstract

Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young people with poor prognosis. At present, the mechanisms underlying tumorigenesis in OS are not well understood. The methionine adnosyltransferase 2B (MAT2B) gene encodes the regulatory subunit of methionine adenosyltransferase (MAT). Recent studies demonstrated that it is highly expressed in a number of human malignancies; however, is undefined in OS. In the present study, MAT2B expression was investigated in tumor samples and cell lines. In vivo and in vitro, lentivirus-mediated small hairpin RNA was constructed to target the MAT2B gene and examine the role of MAT2B in OS proliferation. Microarray analysis was performed to examine the possible downstream molecular target of MAT2B in OS. MAT2B was markedly increased in OS specimens compared with the normal bone tissues, and it was additionally abundantly expressed in OS cell lines. Inhibition of MAT2B expression caused a marked decrease in proliferation and significant increase in apoptosis. In vivo, MAT2B silencing significantly inhibited OS cell growth. Microarray analysis suggested that epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) may function as downstream targets of MAT2B in OS, as confirmed by reverse transcription-quantitative polymerase chain reaction assays and western blotting. Collectively, these results suggested that MAT2B serves a critical role in the proliferation of OS by regulating EGFR and PCNA and that it may be a potential therapeutic target and prognostic factor of OS.