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微小RNA-200c通过下调叉头框蛋白F2抑制乳腺肿瘤转移。

MiR-200c inhibits metastasis of breast tumor via the downregulation of Foxf2.

作者信息

Zhang T, Wan J G, Liu J B, Deng M

机构信息

Department of General Surgery, , , China.

Department of General Surgery, , , China

出版信息

Genet Mol Res. 2017 Aug 17;16(3):gmr-16-03-gmr.16038971. doi: 10.4238/gmr16038971.

Abstract

The forkhead box F2 (Foxf2) gene suppresses epithelial-mesenchymal transition via the modulation of transcription of zinc finger E-box-binding homeobox 1 (Zeb1) and epithelial (E)-cadherin, thereby inhibiting tumor metastasis. Additionally, the specific binding of microRNA (miR)-200c to Foxf2 mRNA impedes metastatic pulmonary cancer. However, the role of miR-200c in breast cancer is still unknown. Therefore, in this study, miR-200c mimics were transfected into the highly metastatic breast cancer cell line MDA-MB-231. Their invasion and migration abilities were observed by scratch and transwell migration assays. Real-time PCR was used to detect mRNA levels of Foxf2, Zeb1, and E-cadherin, whereas Foxf2 protein level was determined by western blot analysis. Our results showed that, compared to the control group, miR-200c inhibited the migration or invasion of MDA-MB-231 cells. Real-time PCR and western blot analysis exhibited significant decreases in Foxf2 expression in the presence of miR-200c, along with a decrease in Zeb1 and increase in E-cadherin mRNA expressions. Thus, our preliminary data demonstrated that miR-200c could inhibit the metastasis of breast cancer cells by downregulating Foxf2 expression, providing leads for the discovery of a novel breast cancer treatment.

摘要

叉头框F2(Foxf2)基因通过调节锌指E盒结合同源框1(Zeb1)和上皮(E)-钙黏蛋白的转录来抑制上皮-间质转化,从而抑制肿瘤转移。此外,微小RNA(miR)-200c与Foxf2 mRNA的特异性结合可阻碍转移性肺癌。然而,miR-200c在乳腺癌中的作用仍不清楚。因此,在本研究中,将miR-200c模拟物转染到高转移性乳腺癌细胞系MDA-MB-231中。通过划痕和Transwell迁移试验观察其侵袭和迁移能力。采用实时定量PCR检测Foxf2、Zeb1和E-钙黏蛋白的mRNA水平,而Foxf2蛋白水平则通过蛋白质印迹分析来确定。我们的结果表明,与对照组相比,miR-200c抑制了MDA-MB-231细胞的迁移或侵袭。实时定量PCR和蛋白质印迹分析显示,在存在miR-200c的情况下,Foxf 的表达显著降低,同时Zeb1表达降低,E-钙黏蛋白mRNA表达增加。因此,我们的初步数据表明,miR-200c可通过下调Foxf2表达来抑制乳腺癌细胞的转移,为发现新的乳腺癌治疗方法提供了线索。

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