miR-665 inhibits epithelial-to-mesenchymal transition in bladder cancer via the SMAD3/SNAIL axis
Weiyu Wang, Yufan Ying, Haiyun Xie, Jiangfeng Li, Xueyou Ma, Liujia He, Mingjie Xu, Shiming Chen, Haixiang Shen, Xiangyi Zheng, Ben Liu, Xiao Wang, Liping Xie
Abstract
Emerging research indicates that miRNAs can regulate cancer progression by influencing molecular pathways. Here, we studied miR-665, part of the DLK1-DIO3 miRNA cluster, which is downregulated by upstream methylation in bladder cancer. MiR-665 overexpression significantly downregulated the expression of SMAD3, phospho-SMAD3, and SNAIL, reversed epithelial-mesenchymal transition progression, and inhibited the migration of bladder cancer cells. To predict potential targets of miR-665, we used online databases and subsequently determined that miR-665 binds directly to the 3' untranslated region of SMAD3. Moreover, silencing of SMAD3 with small interfering RNAs phenocopied the effect of miR-665 overexpression, and overexpression of SMAD3 restored miR-665-overexpression-induced metastasis. This study revealed the role of the miR-665/SMAD3/SNAIL axis in bladder cancer, as well as the potential of miR-665 as a promising therapeutic target.