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An estrogen receptor α suppressor, microRNA‐22, is downregulated in estrogen receptor α‐positive human breast cancer cell lines and clinical samples
Author(s) -
Xiong Jianhua,
Yu Dianke,
Wei Na,
Fu Hanjiang,
Cai Tianjing,
Huang Yuanyu,
Wu Chen,
Zheng Xiaofei,
Du Quan,
Lin Dongxin,
Liang Zicai
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07594.x
Subject(s) - microrna , estrogen receptor , cancer research , biology , estrogen receptor alpha , gene silencing , carcinogenesis , estrogen receptor beta , hek 293 cells , cell growth , breast cancer , small interfering rna , transfection , cancer , cell culture , microbiology and biotechnology , genetics , gene
Previous studies have suggested that microRNAs (miRNAs) may play important roles in tumorigenesis, but little is known about the functions of most miRNAs in cancer development. In the present study, we set up a cell‐based screen using a luciferase reporter plasmid carrying the whole ∼ 4.7 kb 3′‐UTR of estrogen receptor α (ERα) mRNA cotransfected with a synthetic miRNA expression library to identify potential ERα‐targeting miRNAs. Among all the miRNAs, miR‐22 was found to repress robustly the luciferase signal in both HEK‐293T and ERα‐positive MCF‐7 cells. Mutation of the target site was found to abrogate this repression effect of miR‐22, whereas antagonism of endogenous miR‐22 in MDA‐MB‐231 cells resulted in elevated reporter signals. We assessed the miR‐22 expression patterns in five breast cancer cell lines and 23 clinical biopsies and revealed that there is a significant inverse association between the miR‐22 levels and ERα protein expression. To evaluate the potential of miR‐22 as a potential therapeutic intervention, we found that reduction of endogenous ERα protein levels and suppression of cancer cell growth could be achieved in MCF‐7 cells by miR‐22 overexpression in a way that can be recapitulated by the introduction of specific small interfering RNA against ERα. The phenomena can be rescued by the reintroduction of ERα. Taken together, our data indicate that miR‐22 was frequently downregulated in ERα‐positive human breast cancer cell lines and clinical samples. Direct involvement in the regulation of ERα may be one of the mechanisms through which miR‐22 could play a pivotal role in the pathogenesis of breast cancer.