title: TRIM66 overexpresssion contributes to osteosarcoma carcinogenesis and indicates poor survival outcome.
abstract: TRIM66 belongs to the family of tripartite motif (TRIM)-containing proteins. Alterations in TRIM proteins have been implicated in several malignancies. This study was aimed at elucidating the expression and biological function of TRIM66 in osteosarcoma. Here, TRIM66 expression level was higher in osteosarcoma tissues than in normal tissues. High TRIM66 expression was correlated with high rate of local recurrence and lung metastasis, and short survival time. Then, we found that knockdown of TRIM66 in two osteosarcoma cell lines, MG63 and HOS, significantly inhibited cell proliferation and induced G1-phase arrest. Moreover, inhibition of TRIM66 in osteosarcoma cells significantly induced cell apoptosis, while remarkably inhibited cell migration, invasion as well as tumorigenicity in nude mice. Gene set enrichment analysis in Gene Expression Omnibus dataset revealed that apoptosis, epithelial-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling pathway-related genes were enriched in TRIM66 higher expression patients, which was confirmed by western blot analysis in osteosarcoma cells with TRIM66 silenced. In conclusion, TRIM66 may act as an oncogene through suppressing apoptosis pathway and promoting TGF-β signaling in osteosarcoma carcinogenesis. TRIM66 may be a prognostic factor and potential therapeutic target in osteosarcoma.
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Haisong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology & Critical Care Medicine, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yin
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009857:Oncogenes / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D023041:Xenograft Model Antitumor Assays
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C000609454:TRIM66 protein, human; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D053179:Caspase 7; D053453:Caspase 9
keywords: EMT; TGF-β; TRIM66; osteosarcoma; p53