title: FBXW7 acts as an independent prognostic marker and inhibits tumor growth in human osteosarcoma.
abstract: F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS.
authors.affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. shrenji@gmail.com.
authors.forename: Zhanchun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. applexiaomz@gmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Anhui Medical University, Anhui 230022, China. kongzhuhu@gmail.com.
authors.forename: Kongzu
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, the Second Affiliated Hospital of Nanjing Medical University, Jiangsu 210029, China. kcb069js@gmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Hangzhou First People's Hospital, Zhejiang 310006, China. maotai5488@gmail.com.
authors.forename: Maoqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. lzctgzyyx@gmail.com.
authors.forename: Jidong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. wly1618@gmail.com.
authors.forename: Guangqi
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism; D018572:Disease-Free Survival; D015536:Down-Regulation; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012516:Osteosarcoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019927:Cyclin E; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D016271:Proto-Oncogene Proteins c-myc; D044767:Ubiquitin-Protein Ligases