Xiaoliang Chen1, Chunshu Jia2, Chunyi Jia3, Xingyi Jin4, Xinquan Gu1. 1. Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, China. 2. Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China. 3. Department of Thoracic Oncosurgery, Jilin Province Cancer Hospital, Changchun, China. 4. Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, China.
Abstract
BACKGROUND/AIMS: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. METHODS: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. RESULTS: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. CONCLUSION: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.
BACKGROUND/AIMS: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. METHODS: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. RESULTS: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancerpatients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP humanbladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. CONCLUSION: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.
Authors: Carlos Perez-Sanchez; Ariana Barbera Betancourt; Paul A Lyons; Zinan Zhang; Chenqu Suo; James C Lee; Eoin F McKinney; Louise K Modis; Christian Ellson; Kenneth G C Smith Journal: J Exp Med Date: 2022-04-01 Impact factor: 14.307