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Cancer Res. 2009 Oct 15;69(20):8157-65. doi: 10.1158/0008-5472.CAN-09-1996. Epub 2009 Oct 13.

microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells.

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  • 1Departments of Pathology and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.

Abstract

microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting. Unbiased microarray analysis combined with bioinformatics identified cell cycle regulator Cdc25A as a miR-21 target. miR-21 suppressed Cdc25A expression through a defined sequence in its 3'-untranslated region. We found that miR-21 is induced by serum starvation and DNA damage, negatively regulates G(1)-S transition, and participates in DNA damage-induced G(2)-M checkpoint through down-regulation of Cdc25A. In contrast, miR-21 deficiency did not affect apoptosis induced by a variety of commonly used anticancer agents or cell proliferation under normal cell culture conditions. Furthermore, miR-21 was found to be underexpressed in a subset of Cdc25A-overexpressing colon cancers. Our data show a role of miR-21 in modulating cell cycle progression following stress, providing a novel mechanism of Cdc25A regulation and a potential explanation of miR-21 in tumorigenesis.

PMID:
19826040
[PubMed - indexed for MEDLINE]
PMCID:
PMC2763324
Free PMC Article
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