TRIM66 overexpresssion contributes to osteosarcoma carcinogenesis and indicates poor survival outcome.
TRIM66 overexpresssion contributes to osteosarcoma carcinogenesis and indicates poor survival outcome.
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DOI：
10.18632/oncotarget.4291
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发表时间：
2015-09-15
期刊：
影响因子：
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通讯作者：
Chen D
中科院分区：
文献类型：
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作者：
Chen Y;Guo Y;Yang H;Shi G;Xu G;Shi J;Yin N;Chen D
TRIM66属于三部基序（TRIM）蛋白家族。TRIM蛋白的改变与几种恶性肿瘤有关。本研究旨在阐明TRIM66在骨肉瘤中的表达及其生物学功能。TRIM66在骨肉瘤组织中的表达水平高于正常组织。TRIM66高表达与局部复发和肺转移率高、生存时间短相关。然后，我们发现在MG63和HOS两种骨肉瘤细胞系中，敲低TRIM66可显著抑制细胞增殖并诱导g1期阻滞。此外，在裸鼠骨肉瘤细胞中抑制TRIM66可显著诱导细胞凋亡，同时显著抑制细胞迁移、侵袭和致瘤性。基因表达Omnibus数据集的基因集富集分析显示，TRIM66高表达患者细胞凋亡、上皮-间充质转化（EMT）和转化生长因子-β (TGF-β)信号通路相关基因富集，这在TRIM66沉默的骨肉瘤细胞中得到了western blot分析的证实。综上所述，TRIM66可能通过抑制细胞凋亡途径，促进TGF-β信号通路在骨肉瘤癌变过程中发挥癌基因作用。TRIM66可能是骨肉瘤的预后因素和潜在的治疗靶点。
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.