title: RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis.
abstract: 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.
authors.affiliation: 1] Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan [2] Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan [3] Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Ryou-U
authors.initials: RU
authors.lastname: Takahashi
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kosaka
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nezu
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
authors.affiliation: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya