title: The tumor suppressive role of RASSF1A in osteosarcoma through the Wnt signaling pathway.
abstract: Ras-association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene and its expression is lost in numerous types of cancer cells, including primary osteosarcoma cells. However, its functional significance in osteosarcoma has not been well defined. The messenger RNA (mRNA) expression of RASSF1A in osteosarcoma tissues and corresponding non-tumoral tissues was measured by real-time PCR. Overexpression of RASSF1A was established by an adenoviral vector expressing RASSF1A. Cell migration and invasion were analyzed in transwells. Apoptosis and cell cycle were analyzed using flow cytometry. Wnt/β-catenin activity was measured by TCF reporter dual-luciferase assay. Cell viability was measured by MTT assay. Protein expression was detected by Western blot. RASSF1A mRNA expression was significantly lower in osteosarcoma tissues than that in the corresponding non-tumoral tissues. The lowered RASSF1A expression correlated with the clinical severity of osteosarcoma. rAd-RASSF1A injection significantly inhibited the growth of xenograft MNNG/HOS tumors in mice. Overexpression of RASSF1A resulted in significant inhibition of the proliferation, migration, and invasion; induced apoptosis; and arrested cell cycle at G0/G1 phase in both the MNNG/HOS and SaOS2 cells. Overexpression of RASSF1A inhibited the Wnt/β-catenin activity, decreased phosphorylation of Akt/glycogen synthase kinase-3-β (GSK3-β), and increased phosphorylation of mammalian sterile 20-like kinase 1 (MST1). Overexpression of RASSF1A downregulated the cyclin D1, c-Myc, and matrix metalloproteinase-7 (MMP-7) protein levels. RASSF1A functions as a tumor suppressor in osteosarcoma and exerts anti-cancer roles through regulating Akt/GSK-3-Wnt/β-catenin signaling.
authors.affiliation: Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South University, 138 Tong Zi Po Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South University, 138 Tong Zi Po Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South University, 138 Tong Zi Po Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Jin-Shen
authors.initials: JS
authors.lastname: He
authors.affiliation: Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South University, 138 Tong Zi Po Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South University, 138 Tong Zi Po Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China. zangxiaofang08@yahoo.com.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Zang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: C411762:RASSF1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins
keywords: Osteosarcoma; RASSF1A; Wnt; β-catenin