Androgen-responsive tripartite motif 36 enhances tumor-suppressive effect by regulating apoptosis-related pathway in prostate cancer.
Androgen-responsive tripartite motif 36 enhances tumor-suppressive effect by regulating apoptosis-related pathway in prostate cancer.
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DOI：
10.1111/cas.13803
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发表时间：
2018-12
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：
Kimura N;Yamada Y;Takayama KI;Fujimura T;Takahashi S;Kume H;Inoue S
TRIM 36（Tripartite motif 36）属于TRIM家族，其大多数成员通过作为E3泛素连接酶而参与靶蛋白的泛素化和降解。TRIM36的功能尚未得到充分的证明，因此，我们研究了TRIM36在人前列腺癌（PC）中的临床意义和功能。多变量逻辑回归分析表明，TRIM 36免疫反应性是PC患者癌症特异性生存的独立预测因素。功能获得研究显示，TRIM36的过表达抑制了LNCaP、22 Rv1和DU 145细胞的细胞增殖和迁移。此外，使用siRNA敲低TRIM36抑制LNCaP和22Rv1细胞中的细胞凋亡并促进细胞增殖和迁移。此外，我们的微阵列分析显示，TRIM36过表达显著上调了凋亡相关通路。TUNEL分析显示，在siTRIM 36处理的LNCaP和22Rv1细胞中，多西他赛处理促进的细胞凋亡减轻。总之，这些结果表明TRIM36的高表达与良好的预后相关，并且TRIM36通过抑制细胞增殖和迁移以及促进PC中的细胞凋亡而发挥肿瘤抑制作用。
Tripartite motif 36 (TRIM36) belongs to the TRIM family, most members of which are involved in ubiquitination and degradation of target proteins by functioning as E3 ubiquitin ligases. The function of TRIM36 has not been well documented, therefore, we investigated the clinical significance and function of TRIM36 in human prostate cancer (PC). Multivariate logistic regression analysis showed that TRIM36 immunoreactivity was an independent predictor of cancer‐specific survival of PC patients. Gain‐of‐function study revealed that overexpression of TRIM36 suppressed cell proliferation and migration of LNCaP, 22Rv1, and DU145 cells. Moreover, TRIM36 knockdown using siRNA suppressed apoptosis and promoted cell proliferation and migration in LNCaP and 22Rv1 cells. Furthermore, our microarray analysis revealed that the apoptosis‐related pathway was significantly upregulated by TRIM36 overexpression. The TUNEL assay showed that apoptosis promoted by docetaxel treatment was alleviated in siTRIM36‐treated LNCaP and 22Rv1 cells. Taken together, these results suggest that high expression of TRIM36 is associated with favorable prognosis and that TRIM36 plays a tumor‐suppressive role by inhibiting cell proliferation and migration as well as promoting apoptosis in PC.
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