Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-β/Smad2/3 signaling pathway in bladder cancer cells.
Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-β/Smad2/3 signaling pathway in bladder cancer cells.
复制标题
沉默 Trim59 通过 TGF-β/Smad2/3 信号通路抑制膀胱癌细胞的侵袭/迁移和上皮间质转化
DOI：
10.2147/ott.s130139
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发表时间：
2017
影响因子：
4
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Chen W;Zhao K;Miao C;Xu A;Zhang J;Zhu J;Su S;Wang Z
编码TRIM蛋白家族的进化保守基因参与多种生物学过程，包括细胞免疫、炎症反应、抗病毒活性和肿瘤进展。该蛋白家族的一个成员Trim 59已被报道为多种人类癌症（如肺癌、胃癌、宫颈癌和骨肉瘤）的发生和进展的新型生物标志物。然而，关于Trim 59与膀胱癌发生的关系知之甚少。在这项研究中，我们检测了Trim 59在膀胱癌（Bca）标本和细胞系中的表达，并研究了其在Bca细胞系中的生物学作用。我们发现Trim 59在Bca组织和细胞系中上调。此外，使用transwell小室分析和细胞划痕试验，我们确定，敲低Trim 59显着抑制上皮间质转化（EMT）和细胞侵袭和迁移的过程中的Bca细胞系。此外，我们发现下调Trim 59表达也可以抑制细胞增殖和促进凋亡。结果表明，Trim 59诱导的Bca细胞EMT和侵袭/迁移的作用是通过激活转化生长因子β/Smad 2/3信号通路实现的。我们的研究结果还表明，Trim 59可以呈现致癌活性，并可能作为膀胱癌治疗的新候选靶点。
The evolutionarily conserved genes that encode the tripartite motif (TRIM) protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis. In this study, we examined the expression of Trim59 in bladder cancer (Bca) specimens and cell lines, and investigated its biological roles in Bca cell lines. We found that Trim59 was upregulated in Bca tissues and cell lines. In addition, using transwell chamber assays and the cell scratch test, we determined that knockdown of Trim59 significantly inhibited the epithelial-mesenchymal transition (EMT) and the processes of cell invasion and migration in Bca cell lines. Furthermore, we found that downregulated Trim59 expression could also inhibit cell proliferation and promote apoptosis. As a result, we demonstrated that the effects of Trim59-induced EMT and invasion/migration in Bca cells were achieved by the activation of the transforming growth factor beta/Smad2/3 signaling pathway. Our findings also revealed that Trim59 can present oncogenic activity, and may serve as a novel candidate target for bladder carcinoma treatment.