miR-665 inhibits epithelial-to-mesenchymal transition in bladder cancer via the SMAD3/SNAIL axis
miR-665 inhibits epithelial-to-mesenchymal transition in bladder cancer via the SMAD3/SNAIL axis
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miR-665通过SMAD3/SNAIL轴抑制膀胱癌上皮间质转化
DOI：
10.1080/15384101.2021.1929677
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发表时间：
2021-07-02
期刊：
影响因子：
4.3
通讯作者：
Xie, Liping
中科院分区：
文献类型：
--
作者：
Wang, Weiyu;Ying, Yufan;Xie, Liping
新兴研究表明，微小RNA（miRNAs）可通过影响分子通路来调控癌症进展。在此，我们研究了miR - 665，它是DLK1 - DIO3微小RNA簇的一部分，在膀胱癌中因上游甲基化而下调。miR - 665过表达显著下调了SMAD3、磷酸化 - SMAD3和SNAIL的表达，逆转了上皮 - 间质转化进程，并抑制了膀胱癌细胞的迁移。为了预测miR - 665的潜在靶点，我们使用了在线数据库，随后确定miR - 665直接结合到SMAD3的3'非翻译区。此外，用小干扰RNA沉默SMAD3可模拟miR - 665过表达的效应，而SMAD3过表达可恢复miR - 665过表达诱导的转移。这项研究揭示了miR - 665 / SMAD3 / SNAIL轴在膀胱癌中的作用，以及miR - 665作为一个有前景的治疗靶点的潜力。
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 3MODIFIER LETTER PRIME 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.