Cofilin 1 promotes bladder cancer and is regulated by TCF7L2.
Cofilin 1 promotes bladder cancer and is regulated by TCF7L2.
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Cofilin 1 促进膀胱癌并受 TCF7L2 调节
DOI：
10.18632/oncotarget.20664
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Wang F;Wu D;Fu H;He F;Xu C;Zhou J;Li D;Li G;Xu J;Wu Q;Chen J;Su L;Wang W;Zhang S
早期的报道表明，Cofilin表达在膀胱癌样本中增加，尽管其功能仍然未知。在此，我们发现Cofilin 1在膀胱癌组织中的表达高于癌旁组织。Cofilin 1的过表达促进T24和RT4膀胱癌细胞系的增殖、迁移和侵袭，而Cofilin 1的敲低抑制T24和RT4膀胱癌细胞系的增殖、迁移和侵袭。此外，在小鼠异种移植实验中，Cofilin 1过表达增加膀胱肿瘤体积，而Cofilin 1敲低降低膀胱肿瘤体积。转录因子7样2（TCF7L2）靶向Cofilin 1基因的启动子，并且TCF7L2敲低或Cofilin 1启动子中的突变显著降低Cofilin 1转录。TCF7L2促进细胞增殖和迁移，并增加RT4和T24细胞中Cofilin 1蛋白水平。因此，TCF7L2通过结合Cofilin 1启动子并增加其表达而促进Cofilin 1诱导的膀胱癌发展。
Earlier reports demonstrated that Cofilin expression is increased in bladder cancer samples, though its function remains unknown. Here, we found that Cofilin 1 expression was higher in bladder cancer tissues than in paracancerous tissues. Overexpression of Cofilin 1 promoted, while Cofilin 1 knockdown inhibited, proliferation, migration, and invasion in the T24 and RT4 bladder cancer cell lines. In addition, Cofilin 1 overexpression increased, while Cofilin 1 knockdown decreased, bladder tumor volumes in mouse xenograft experiments. Transcription factor 7-like 2 (TCF7L2) targeted the promoter of the Cofilin 1 gene, and TCF7L2 knockdown or mutations in the Cofilin 1 promoter dramatically decreased Cofilin 1 transcription. TCF7L2 promoted cell proliferation and migration and increased Cofilin 1 protein levels in RT4 and T24 cells. Thus, TCF7L2 contributed to Cofilin 1-induced promotion of bladder cancer development by binding to the Cofilin 1 promoter and increasing its expression.