Yaoyao Xiong1, Xiongbing Zu2, Long Wang2, Yuan Li2, Minfeng Chen2, Wei He3, Lin Qi2. 1. Department of Cardiopulmonary Bypass, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China. 2. Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China. 3. Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China. xy_heweidoctor@163.com.
Abstract
BACKGROUND: Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial-mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer. METHODS: Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells. RESULTS: Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis. CONCLUSIONS: In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.
BACKGROUND:Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial-mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer. METHODS: Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells. RESULTS: Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis. CONCLUSIONS: In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.
Authors: Maria C Rangel; Hideaki Karasawa; Nadia P Castro; Tadahiro Nagaoka; David S Salomon; Caterina Bianco Journal: Am J Pathol Date: 2012-04-26 Impact factor: 4.307
Authors: Frederikke Lihme Egerod; Annette Bartels; Niels Fristrup; Michael Borre; Torben F Ørntoft; Martin B Oleksiewicz; Nils Brünner; Lars Dyrskjøt Journal: BMC Cancer Date: 2009-10-30 Impact factor: 4.430