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.
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.


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.
['Jiang|Zhenming|Z|', 'Zhang|Yuxi|Y|0000-0003-1802-6754', 'Chen|Xi|X|', 'Wu|Pingeng|P|', 'Chen|Dong|D|']
Wnt/β-catenin signaling pathway microRNA-129-5p Angiogenesis Prostate cancer Epithelial–mesenchymal transition Zinc-finger protein of the cerebellum 2