Qi Li, Lu Zhong, Sun Yong-Hong, Song Hai-Tao, Xu Wei-Kang
Clinical College of Weifang Medical University, Weifang, Shandong 261031, P.R. China.
Int J Mol Med. 2016 Dec;38(6):1734-1742. doi: 10.3892/ijmm.2016.2774. Epub 2016 Oct 17.
Prostate carcinoma is a devastating disease which is characterized by insidious early symptoms, rapid progression and a poor prognosis. Tripartite motif-containing protein 16 (TRIM16) was identified as an estrogen- and antiestrogen-regulated gene in epithelial cells stably expressing estrogen receptors. The protein encoded by this gene contains two B-box domains and a coiled-coiled region that are characteristic of the B-box zinc finger protein family. Proteins belonging to this family have been reported to be involved in a variety of biological processes including cell growth, differentiation and pathogenesis. TRIM16 expression has been detected in most tissues. However, the funtions of this gene remain to be elucidated. In the present study, immunohistochemical staining revealed that the expression of TRIM16 was decreased in prostate adenocarcinoma compared with that in normal prostate tissues. The patients with high TRIM16-expressing tumors had a significantly greater survival than those with low TRIM16-expressing tumors. Western blot analysis showed that TRIM16 was downregulated in distant metastatic cancer tissues compared with that in non-distant metastatic cancer tissues. The overexpression of TRIM16 inhibited the migration and invasion of prostate cancer cells as well as inhibiting the epithelial-to-mesenchymal transition process, whereas TRIM16 depletion enhanced these processes. Moreover, TRIM16 inhibited the Snail signaling pathway. The silencing of Snail by small interfering RNA was performed in order to determine the role of Snail in the TRIM16-mediated tumor phenotype. Taken together, these findings suggest that TRIM16 may be an important molecular target which may aid in the design of novel therapeutic agents for prostate cancer.
前列腺癌是一种具有隐匿性早期症状、进展迅速且预后不良等特征的毁灭性疾病。含三联基序蛋白16（TRIM16）在稳定表达雌激素受体的上皮细胞中被鉴定为雌激素和抗雌激素调节基因。该基因编码的蛋白质包含两个B盒结构域和一个卷曲螺旋区域，这些是B盒锌指蛋白家族的特征。据报道，属于该家族的蛋白质参与多种生物学过程，包括细胞生长、分化和发病机制。TRIM16在大多数组织中都有表达。然而，该基因的功能仍有待阐明。在本研究中，免疫组织化学染色显示，与正常前列腺组织相比，TRIM16在前列腺腺癌中的表达降低。TRIM16高表达肿瘤患者的生存率明显高于TRIM16低表达肿瘤患者。蛋白质印迹分析表明，与非远处转移癌组织相比，TRIM16在远处转移癌组织中表达下调。TRIM16的过表达抑制前列腺癌细胞的迁移和侵袭以及上皮-间质转化过程，而TRIM16的缺失则增强了这些过程。此外，TRIM16抑制Snail信号通路。为了确定Snail在TRIM16介导的肿瘤表型中的作用，进行了小干扰RNA沉默Snail的实验。综上所述，这些发现表明TRIM16可能是一个重要的分子靶点，有助于设计新型前列腺癌治疗药物。
