Qi Zeng-Xin, Cai Jia-Jun, Chen Ling-Chao, Yue Qi, Gong Yan, Yao Yu, Mao Ying
Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
Department of Geriatrics, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
J Neurooncol. 2016 Jan;126(1):19-26. doi: 10.1007/s11060-015-1897-8.
Tripartite motif (TRIM) proteins are involved in tumorigenesis. Here, we examined the expression, biological function, and clinical significance of tripartite motif containing 28 (TRIM28) in glioma, a locally aggressive brain tumor. First, TRIM28 expression was significantly higher in glioma (n = 138) than in non-glioma controls (n = 6). TRIM28 expression was positively correlated with tumor malignancy, and associated with poor overall survival (OS) and progression-free survival (PFS). Notably, TRIM28 expression was negatively correlated with p21 expression in patients with glioblastoma multiforme (GBM). A multivariate analysis that included relevant measures indicated that high TRIM28 expression is an independent prognostic factor for poor OS and PFS in GBM patients. In experiments with cultured glioma cells, down-regulating TRIM28 with shRNA increased p21 expression, and induced cell cycle arrest at the G1 phase. In a xenograft model, down-regulating TRIM28 suppressed tumor growth. These results indicate that over-expression of TRIM28 is associated with poor outcome in glioma patients.
三聚体基序(TRIM)蛋白参与肿瘤发生。在此,我们研究了含28个三聚体基序(TRIM28)在胶质瘤(一种局部侵袭性脑肿瘤)中的表达、生物学功能及临床意义。首先,TRIM28在胶质瘤(n = 138)中的表达显著高于非胶质瘤对照(n = 6)。TRIM28表达与肿瘤恶性程度呈正相关,并与总生存期(OS)和无进展生存期(PFS)较差相关。值得注意的是,在多形性胶质母细胞瘤(GBM)患者中,TRIM28表达与p21表达呈负相关。一项纳入相关指标的多因素分析表明,TRIM28高表达是GBM患者OS和PFS较差的独立预后因素。在培养的胶质瘤细胞实验中,用短发夹RNA(shRNA)下调TRIM28可增加p21表达,并诱导细胞周期阻滞于G1期。在异种移植模型中,下调TRIM28可抑制肿瘤生长。这些结果表明,TRIM28过表达与胶质瘤患者的不良预后相关。