A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.
A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.
复制标题
一种新型的预后因子TRIM44促进细胞增殖和迁移，并抑制睾丸生殖细胞肿瘤中的凋亡。
DOI：
10.1111/cas.13105
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发表时间：
2017-01
期刊：
影响因子：
5.7
通讯作者：
Inoue S
中科院分区：
文献类型：
--
作者：
Yamada Y;Takayama KI;Fujimura T;Ashikari D;Obinata D;Takahashi S;Ikeda K;Kakutani S;Urano T;Fukuhara H;Homma Y;Inoue S
TRIM 44是TRIM家族蛋白中的一员，通过调节E3泛素连接酶参与靶蛋白的泛素化和降解。TRIM44过表达已在多种癌症中观察到。然而，其与睾丸生殖细胞肿瘤（TGCT）的关系尚不清楚。本研究旨在探讨TRIM44在TGCT中的作用及其临床意义。TRIM44的高表达与甲胎蛋白水平、临床分期、非恶性生殖细胞肿瘤（NSGCT）和癌症特异性生存率显著相关（分别为P = 0.0009、P = 0.0035、P = 0.0004和P = 0.0140）。多变量分析显示，阳性TRIM44 IR是癌症特异性死亡率的独立预测因子（P = 0.046）。功能获得研究表明，TRIM 44的过表达促进了NTERA 2和NEC 8细胞的细胞增殖和迁移。在这些细胞中，使用siRNA敲低TRIM44促进凋亡并抑制细胞增殖和迁移。NTERA 2细胞的微阵列分析显示，与对照细胞相比，TRIM 44敲低细胞中的肿瘤抑制基因如CADM1、CDK19和PRKACB上调。相反，致癌基因包括C3AR 1，ST3GAL5和NT5E在这些细胞中下调。这些结果表明TRIM44的高表达与不良预后相关，并且TRIM44在TGCT中的细胞增殖、迁移和抗凋亡中起重要作用。
Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor (TGCT) is unknown. We aimed to investigate the clinical significance of TRIM44 and its function in TGCT. High expression of TRIM44 was significantly associated with α feto‐protein levels, clinical stage, nonseminomatous germ cell tumor (NSGCT), and cancer‐specific survival (P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM44 IR was an independent predictor of cancer‐specific mortality (P = 0.046). Gain‐of‐function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1,CDK19, and PRKACB were upregulated in TRIM44‐knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1,ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti‐apoptosis in TGCT.