MiR-27a promotes EMT in ovarian cancer through active Wnt/��-catenin signalling by targeting FOXO1
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Published on: June 17, 2014
Li-Ya Zhang1, Yuan Chen2, Jue Jia3
1Department of Gynecology, Huizhou No. 2 Women's and Children's Healthcare Hospital, Huizhou, Guangdong 516001, China.
Background:
Ovarian cancer (OC) is the fifth most common type of cancer in women worldwide. MiR-27a plays an important role in the development of ovarian cancer. However, the exact function and molecular mechanism of miR-27a in epithelial-mesenchymal transition (EMT) has not been thoroughly elucidated to date.
Methods:
Quantitative real-time PCR (qRT-PCR) was used to determine the expression of miR-27a and FOXO1 mRNA in ovarian tissues and cells. The function of miR-27a in ovarian cancer was investigated through overexpression and knockdown of miR-27a in vitro. Wound healing and Transwell assays were performed to evaluate the migration and invasive capacity of the cells. A luciferase reporter assay was conducted to confirm the interaction between miR-27a and FOXO1. Western blotting was used to evaluate FOXO1, EMT and Wnt/β-catenin relative protein expression.
Results:
In our study, we found that the mRNA expression level of miR-27a was significantly higher in ovarian cancer tissues and in HO8910 and OV90 cells. Functional experiments showed that miR-27a overexpression potentiated the migration and invasion of HO8910 and OV90 cells, while miR-27a inhibition reduced the cells' migration and invasion. Moreover, miR-27a upregulated the expression of mesenchymal cell markers and downregulated the expression of epithelial cell markers, which were restored via silencing of miR-27a expression. Subsequently, miR-27a was found to directly target and suppress the expression of FOXO1. Finally, we demonstrated that miR-27a promoted the progression of ovarian cancer cells and induced the process of EMT via the Wnt/β-catenin signalling pathway through inhibition of FOXO1.
Conclusions:
Taken together, these results indicate that targeting miR-27a and FOXO1 could represent a strategy for anticancer therapy in ovarian cancer.
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