DRP5 is involved in cancer cell growth and predicts poor prognosis in human osteosarcoma

Abstract

Abstract Osteosarcoma is an extremely aggressive primary malignant bone tumor of childhood. Collapsin response mediator proteins ( CRMP s), which are highly expressed in the developing nervous system, were recently shown to be associated with cancer development. However, the relationship between DRP 5 ( CRMP 5) and osteosarcoma has not been evaluated. In this study, we investigated the role of DRP 5 in the regulation of osteosarcoma growth. DRP 5 mRNA and protein levels were significantly upregulated in human osteosarcoma cell lines and associated with increased migration and invasion. Genetic knockdown of DRP 5 markedly suppressed the expression of matrix metalloproteinase ( MMP )‐2 and MMP ‐9. DRP 5 silencing significantly inhibited osteosarcoma cell growth in vitro and in a xenograft mouse model in vivo. Microarray immunohistochemical analysis of osteosarcoma specimens and Kaplan–Meier analysis showed that patients with high DRP 5 protein expression had shorter overall survival than those with low DRP 5 levels. Taken together, these results suggest that DRP 5 plays a critical role in the regulation of osteosarcoma and could be a potential therapeutic target and prognostic factor in osteosarcoma.