Promotional effect of microRNA-194 on breast cancer cells via targeting F-box/WD repeat-containing protein 7

microRNA-194 通过靶向 F-box/WD 重复蛋白 7 对乳腺癌细胞发挥促进作用

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作者:Yaomin Chen, Haiyan Wei, Yu Liu, Shusen Zheng

Abstract

Breast cancer is the most common type of malignant cancer in females. An increasing number of studies have revealed that microRNAs (miR), which belong to a class of small non-coding RNAs, serve an important role in a number of human cancer subtypes. In the present study, the role of miR-194 in breast cancer cells and its underlying mechanisms were investigated. The results demonstrated that the serum levels of miR-194 were significantly higher in patients of the poorly differentiated and well-differentiated groups, compared with in healthy adults. Additionally, the serum level of miR-194 was significantly higher in the poorly differentiated group compared with in the well-differentiated group. In order to further investigate the role of miR-194 in breast cancer cells, the present study transfected two breast cancer cell lines, MCF-7 and MDA-MB-231, with an empty vector (control), miR-194 (overexpression), antagomiR-194 (inhibitor, functional knock down) or antagomiR-194 and miR-194. An MTT assay was performed in order to detect the proliferation of breast cancer cells in the various groups. The results revealed that the overexpression of miR-194 significantly accelerated cell proliferation, whereas the inhibition of miR-194 significantly decelerated the proliferation of MCF-7 and MDA-MB-231 cells. Furthermore, the expression levels of cyclin D and cyclin E were significantly upregulated in miR-194 overexpressing cells, and the expression levels of cyclin D and cyclin E were significantly downregulated in miR-194 inhibited cells, as compared with in control cells. No significant change was observed in the level of proliferation of cells co-transfected with miR-194 and antagomiR-194, compared with in the control cells. According to the hypothesis suggesting possible target genes of miR-194, the present study proposed that F-box/WD repeat-containing protein 7 (Fbxw-7) may be a direct target of miR-194, which was confirmed by a luciferase reporter assay. The present study suggested that miR-194 expression promoted the proliferation of breast cancer cells by targeting Fbxw-7, and may serve as a biomarker and a novel target for breast cancer therapy.

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