Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial-mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

通过靶向 ZIC2,Wnt/β-catenin 信号通路失活是 microRNA-129-5p 抑制前列腺癌上皮间质转化和血管生成的基础

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作者:Zhenming Jiang, Yuxi Zhang, Xi Chen, Pingeng Wu, Dong Chen

Background

Prostate cancer (PCa) is a common disease that often occurs among older men and a frequent cause of malignancy associated death in this group. microRNA (miR)-129-5p has been identified as an essential regulator with a significant role in the prognosis of PC. Therefore, this study aimed to investigate roles of miR-129-5p in PCa.

Conclusions

The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial-mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.

Methods

Microarray analysis was conducted to identify PCa-related genes. The expression of miR-129-5p and ZIC2 in PCa tissues was investigated. To understand the role of miR-129-5p and ZIC2 in PCa, DU145 cells were transfected with mimic or inhibitor of miR-129-5p, or si-ZIC2 and the expression of Wnt, β-catenin, E-cadherin, vimentin, N-cadherin, vascular endothelial growth factor (VEGF), and CD31, as well as the extent of β-catenin phosphorylation was determined. In addition, cell proliferation, migration, invasion, angiogenesis, apoptosis and tumorigenesis were detected.

Results

miR-129-5p was poorly expressed and ZIC2 was highly expressed in PCa tissues. Down-regulation of ZIC2 or overexpression of miR-129-5p reduced the expression of ZIC2, Wnt, β-catenin, N-cadherin, vimentin, and β-catenin phosphorylation but increased the expression of E-cadherin. Importantly, miR-129-5p overexpression significantly reduced cell migration, invasion, angiogenesis and tumorigenesis while increasing cell apoptosis. Conclusions: The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial-mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.

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