Drug resistance and
metastasis are lethal characteristics of
tumors. We previously demonstrated that silencing of
ribophorin II (RPN2), which is part of the N-oligosaccharyl
transferase complex, efficiently induced apoptosis and reduced resistance to
docetaxel in human
breast cancer cells. Here, we report the clinical and functional correlations of RPN2 expression in
osteosarcoma. Immunohistochemical evaluation of 35
osteosarcoma patient biopsies revealed that RPN2 was moderately to highly expressed in all specimens, and higher RPN2
mRNA expression was significantly correlated with poor prognosis. To investigate whether lethal phenotypes of
osteosarcoma could be reduced by regulating the expression of RPN2, we conducted a study of RNAi-induced RPN2 knockdown in highly metastatic human
osteosarcoma cells. The results indicated that RPN2 silencing reduced cell proliferation, sphere formation, cell invasion, and sensitized
drug response in vitro. Mice bearing RPN2-silenced highly metastatic
osteosarcoma xenografts showed reduced
tumor growth and lung
metastasis, and survived longer than mice bearing control
tumor xenografts. Taken together, our data suggest that RPN2 silencing contributes to regulation of lethal
osteosarcoma phenotypes and could be a novel target for
RNAi-based therapeutics against
osteosarcoma.