miR‐4500 suppresses cell proliferation and migration in bladder cancer via inhibition of STAT3/CCR7 pathway

Autor: Na Dong, Zhihua Ye, Xintai Zhong, Dingwen Gui, Wei Peng, Shihao Wu, Haixia Wu
Rok vydání: 2019
Předmět:
Zdroj: Journal of Cellular Biochemistry. 121:3913-3922
ISSN: 1097-4644
0730-2312
Popis: Bladder cancer (BC) is a prevalent type of cancer that occurs in human urinary system threatening the human health. microRNA-4500 (miRNA-4500) is a novel miRNA that serves as a potential biomarker in several types of cancers. However, the in-depth molecular mechanism of miR-4500 in BC has not yet been fully elucidated. Quantitative real-time polymerase chain reactionq and Western blot analysis were applied to analyze the expressions of miR-4500, STAT3, and C-C chemokine receptor 7 (CCR7). Gain-of-function assays involving Cell Counting Kit-8, 5'-ethynyl-2'-deoxyuridine incorporation assay, and Transwell were employed to evaluate miR-4500 function in cell proliferation and migration. Moreover, chromatin immunoprecipitation, RNA immunoprecipitation, and luciferase reporter assay were performed to explore the molecular mechanism underlying function of miR-4500. We found the downregulation of miR-4500 in BC cells, and ectopic expression of miR-4500 hampered cell proliferation, migration, and epithelial-to-mesenchymal transition. Importantly, miR-4500 directly targeted STAT3 3'-untranslated region, leading to repression on STAT3 expression. Intriguingly, STAT3 transcriptionally regulated CCR7. Rescue experiments validated the presence of miR-4500/STAT3/CCR7 axis in control of BC growth and progression. Our data highlighted miR-4500 as a potent cancericidal gene in BC, and might provide a theoretical grounding for development of target-oriented therapies of patients afflicted with BC.
Databáze: OpenAIRE
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