RPN2 gene confers osteosarcoma cell malignant phenotypes and determines clinical prognosis

Tomohiro Fujiwara, Ryou U. Takahashi, Nobuyoshi Kosaka, Yutaka Nezu, Akira Kawai, Toshifumi Ozaki, Takahiro Ochiya

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 relationships 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.

Original languageEnglish
Article numbere189
Pages (from-to)e189
JournalMolecular Therapy - Nucleic Acids
Volume3
DOIs
Publication statusPublished - Aug 26 2014

Keywords

  • Drug response
  • Metastasis
  • Osteosarcoma
  • RNA interference
  • Ribophorin II (RPN2)

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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