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MicroRNA‐125b suppresses the development of bladder cancer by targeting E2F3
Author(s) -
Huang Li,
Luo Junhua,
Cai Qingqing,
Pan Qiuhui,
Zeng Hong,
Guo Zhenghui,
Dong Wen,
Huang Jian,
Lin Tianxin
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25509
Subject(s) - carcinogenesis , bladder cancer , microrna , cancer research , downregulation and upregulation , cancer , biology , urothelium , transfection , cell cycle , cell growth , cell culture , endocrinology , gene , genetics , urinary system
Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to tumorigenesis. microRNA‐125b (miR‐125b) was implicated to have close relationship with cell proliferation and differentiation, and downregulation of miR‐125b was observed in various types of cancers. However, the biological function of miR‐125b in bladder tumorigenesis is still unknown. In our study, we showed that the expression of miR‐125b was significantly decreased in bladder cancer tissues and four bladder cancer cell lines. Moreover, miR‐125b could suppress bladder cancer cells to form colonies in vitro and to develop tumors in nude mice. E2F3, which was critical for G1/S transition and was overexpressed in most of poor‐differentiated bladder cancers, was identified as a target of miR‐125b by luciferase assay. The E2F3 mRNA and protein expression levels were detected in bladder cancer tissues and cell lines, and interestingly, inverse correlations between miR‐125b and E2F3 protein level were found in bladder cancer tissues and four E2F3 nonamplified cell lines. Introduction of miR‐125b could reduce the expression of E2F3 protein but not the E2F3 mRNA. In addition, we observed that transfection of miR‐125b could inhibit the expression of Cyclin A2, one of the E2Fs‐responsive genes involved in G1/S transition. These results suggest that miR‐125b may regulate G1/S transition through the E2F3–Cyclin A2 signaling pathway. Taken together, miR‐125b may act as a tumor suppressor in bladder urothelium, and downregulation of miR‐125b may contribute to the tumorigenesis of bladder cancer.