Wang Fei, Wu Dinglan, Fu Housheng, He Fengrong, Xu Congjie, Zhou Jiaquan, Li Daoyuan, Li Guoping, Xu Jianbing, Wu Qinghui, Chen Jianxiang, Su Liangju, Wang Weifu, Zhang Shufang
Department of Urology, People's Hospital of Hainan Province, Haikou, China.
The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Oncotarget. 2017 Sep 6;8(54):92043-92054. doi: 10.18632/oncotarget.20664. eCollection 2017 Nov 3.
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.
早期报告显示，在膀胱癌样本中Cofilin的表达增加，但其功能仍不清楚。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的过表达促进了T24和RT4膀胱癌细胞系的增殖、迁移和侵袭，而Cofilin 1的敲低则抑制了这些过程。此外，在小鼠异种移植实验中，Cofilin 1的过表达增加了膀胱肿瘤体积，而Cofilin 1的敲低则减小了膀胱肿瘤体积。转录因子7样2（TCF7L2）靶向Cofilin 1基因的启动子，TCF7L2的敲低或Cofilin 1启动子中的突变显著降低了Cofilin 1的转录。TCF7L2促进了RT4和T24细胞的增殖和迁移，并增加了Cofilin 1蛋白水平。因此，TCF7L2通过与Cofilin 1启动子结合并增加其表达，促进了Cofilin 1诱导的膀胱癌发展。
