Xie FeiYan, Hosany Sumayyah, Zhong Shen, Jiang Yang, Zhang Fen, Lin LiLi, Wang XiaoBo, Gao ShenMeng, Hu XiaoQu
Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
PLoS One. 2017 Oct 10;12(10):e0185565. doi: 10.1371/journal.pone.0185565. eCollection 2017.
In many cancers, microRNA-193a (miR-193a) is a suppressor miRNA, but its underlying anti-oncogenic activity in breast cancer is not known. In this study, we found decreased miR-193a (specifically, miR-193a-5p) expression not only in breast cancer cell lines but also in breast cancer tissues as compared with the adjacent non-tumor tissues. Ectopic miR-193a overexpression inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and BT549 cells. miR-193a reduced Wilms' tumor 1 (WT1) expression and repressed luciferase reporter activity by binding WT1 coding region sequences; mutation of the predicted miR-193a binding site abolished this effect. miR-193a and WT1 expression were significantly inversely correlated in breast cancer tissues. Importantly, the anti-cancer activity induced by miR-193a was partially reversed by WT1 overexpression, indicating an important role for WT1 in such activity related to miR-193a. Our results reveal that miR-193a-WT1 interaction plays an important role in breast cancer metastasis, and suggest that restoring miR-193a expression is a therapeutic strategy in breast cancer.
在许多癌症中,微小RNA-193a(miR-193a)是一种抑癌性微小RNA,但它在乳腺癌中的潜在抗癌活性尚不清楚。在本研究中,我们发现与相邻的非肿瘤组织相比,miR-193a(具体而言,miR-193a-5p)不仅在乳腺癌细胞系中表达降低,在乳腺癌组织中也表达降低。异位过表达miR-193a可抑制MDA-MB-231和BT549细胞的增殖、集落形成、迁移和侵袭。miR-193a通过结合威尔姆斯瘤1(WT1)编码区序列降低WT1表达并抑制荧光素酶报告基因活性;预测的miR-193a结合位点的突变消除了这种作用。在乳腺癌组织中,miR-193a和WT1表达显著负相关。重要的是,WT1过表达部分逆转了miR-193a诱导的抗癌活性,表明WT1在与miR-193a相关的这种活性中起重要作用。我们的结果表明,miR-193a-WT1相互作用在乳腺癌转移中起重要作用,并提示恢复miR-193a表达是乳腺癌的一种治疗策略。