Premium
miR‐4500 suppresses cell proliferation and migration in bladder cancer via inhibition of STAT3/CCR7 pathway
Author(s) -
Peng Wei,
Dong Na,
Wu Shihao,
Gui Dingwen,
Ye Zhihua,
Wu Haixia,
Zhong Xintai
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29558
Subject(s) - chromatin immunoprecipitation , microrna , cell growth , cancer research , ectopic expression , downregulation and upregulation , biology , microbiology and biotechnology , cell culture , gene expression , gene , genetics , promoter
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.