Zhenming Jiang1, Yuxi Zhang2,3, Xi Chen4, Pingeng Wu1, Dong Chen5. 1. Department of Urology, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China. 2. Department of Urology, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China. zyxfan@sina.com. 3. Department of Urology, People's Hospital of Datong Hui and Tu Autonomous County, No. 1, Wenhua Road, Qiaotou Town, Datong Hui and Tu Autonomous County, Xining, 810100, Qinghai, People's Republic of China. zyxfan@sina.com. 4. Department of Pharmacy, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China. 5. Central Lab, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Abstract
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.
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.
Keywords:
Angiogenesis; Epithelial–mesenchymal transition; Prostate cancer; Wnt/β-catenin signaling pathway; Zinc-finger protein of the cerebellum 2; microRNA-129-5p
Authors: Christelle P El-Haibi; Rajesh Singh; Pranav Gupta; Praveen K Sharma; Krysta N Greenleaf; Shailesh Singh; James W Lillard Journal: J Proteomics Bioinform Date: 2012