Xiang Yuan, Liao Xing-Hua, Yao Ao, Qin Huan, Fan Li-Juan, Li Jia-Peng, Hu Peng, Li Hui, Guo Wei, Li Jun-Yan, Gu Chao-Jiang, Bao Le-Yuan, Zhang Tong-Cun
Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei 430081, PR China.
Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei 430081, PR China.
Exp Cell Res. 2017 Oct 15;359(2):394-404. doi: 10.1016/j.yexcr.2017.08.023. Epub 2017 Aug 17.
Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. Our previous study has shown that MRTF-A promote the migration of MDA-MB-231 cells and WDR1 promotes breast cancer cell migration. But the exact molecular mechanism on metastasis is still not fully understood, we now report that WDR1 enhanced the effect of MRTF-A induced-MDA-MB-231 cell migration by promoting the expression of the EMT markers and migration markers via RhoA-MRTF-A signaling pathway. Importantly, WDR1 promoted the nuclear importion of MRTF-A by affecting the expression of nuclear transport protein importin. But WDR1 did not affect the expression of MRTF-A. Interestingly, MRTF-A promoted the expression of miR-206 via its promoter CArG box but miR-206 inhibits the migration of breast cancer cells through suppressing the expression of WDR1 and MRTF-A via targeted their 3'UTR. Our data thus provide important and novel insights into MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration.
乳腺癌是全球女性癌症死亡的主要原因，这与转移密切相关。我们之前的研究表明，MRTF-A促进MDA-MB-231细胞的迁移，而WDR1促进乳腺癌细胞的迁移。但转移的确切分子机制仍未完全了解，我们现在报告，WDR1通过RhoA-MRTF-A信号通路促进EMT标志物和迁移标志物的表达，增强了MRTF-A诱导的MDA-MB-231细胞迁移的作用。重要的是，WDR1通过影响核转运蛋白输入蛋白的表达促进MRTF-A的核输入。但WDR1不影响MRTF-A的表达。有趣的是，MRTF-A通过其启动子CArG盒促进miR-206的表达，但miR-206通过靶向WDR1和MRTF-A的3'UTR抑制其表达，从而抑制乳腺癌细胞的迁移。因此，我们的数据为MRTF-A-miR-206-WDR1形成反馈环调节乳腺癌细胞迁移提供了重要的新见解。
