Lower miR-630 expression predicts poor prognosis of osteosarcoma and promotes cell proliferation, migration and invasion by targeting PSMC2.

Abstract

miR-630 has been reported as a tumor suppressor or tumor promoter in various types of cancer. However, the effect of miR-630 in osteosarcoma (OS) has not been investigated. The purpose of this study was to investigate the expression patterns, clinical value, and functional role of miR-630 in OS. miR-630 levels in 147 paired OS tissues and corresponding normal bone tissues were investigated by RT-PCR. The clinical data were interpreted by chi-square test, Kaplan-Meier analysis, univariate analysis, and multivariate analysis. The functional role of miR-630 was verified using cell experiments. The regulation of Proteasome 26S subunit ATPase 2 (PSMC2) by miR-630 was detected by Western blotting, dual luciferase reporter assays and rescue experiments. We found that miR-630 expression was decreased in OS tissues and cell lines. A low level of miR-630 was associated with advanced clinical stage and distant metastasis. Clinical assay indicated that downregulation of miR-630 strongly correlated with poor prognosis and was an independent prognostic indicator for overall survival of OS patients. Functional investigation showed that miR-630 overexpression inhibited cell growth, colony formation, migration, invasion and EMT pathway, and promoted apoptosis in OS. Mechanistically, miR-630 was identified as direct targets of miR-630 and its overexpression significantly suppressed the levels of PSMC2. In addition, overexpression of PSMC2 recuperated the effects of miR-630 overexpression. Our data indicated that miR-630 targets PSMC2 in OS and inhibited OS cell proliferation, which may offer a new mechanism underlying the development and progression of OS.