title: Nucleosome-binding protein HMGN2 exhibits antitumor activity in human SaO2 and U2-OS osteosarcoma cell lines.
abstract: High mobility group N (HMGNs) are members of the high mobility group protein family, and are involved in the development and progression of several tumors. HMGN1 and HMGN5 were previously shown to be associated with the bioactivities of osteosarcoma. However, the effects and molecular mechanisms of HMGN2 on osteosarcoma progression remain to be determined. In order to characterize the endogenous expression of HMGN2 in osteosarcoma cell lines, RT-PCR and western blot analysis were performed. Recombinant HMGN2 lentivirus was used to infect the osteosarcoma cell lines with relatively low HMGN2 expression to determine the functional relevance of HMGN2 overexpression in osteosarcoma cell growth and migration in vitro and in vivo, and to investigate the expression levels of Ki-67, PCNA, cyclin D1 and cyclin E. The results showed that osteosarcoma cell proliferation and migration were significantly reduced by HMGN2, as indicated by cell count and wound-healing assays. Cell apoptosis was markedly induced and HMGN2 increased the sensitivity to chemotherapy. When HMGN2 expression was enhanced, the expression of cyclin D1 and PCNA was downregulated in osteosarcoma cells. In addition, the tumor volumes in SaO2 and U2-OS subcutaneous nude mouse models treated with HMGN2 lentivirus were significantly decreased as compared to those of the GFP group. These results suggested that the enhanced expression of HMGN2 in osteosarcoma cells by HMGN2 lentivirus, exerts inhibitory effects on growth and migration of osteosarcoma cells.
authors.affiliation: Department of Spine Surgery, Xinchang People's Hospital, Xinchang, Zhejiang 312500, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Enjie
authors.initials: E
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis; D018450:Disease Progression; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D024242:HMGN2 Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D016086:Lentivirus; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015513:Oncogene Proteins / Q000096:biosynthesis; D012516:Osteosarcoma / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C530104:CCND1 protein, human; C475820:CCNE1 protein, human; D019927:Cyclin E; D024242:HMGN2 Protein; D019394:Ki-67 Antigen; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1