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

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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Wang P,Zou F,Zhang X,Li H,Dulak A,Tomko RJ Jr,Lazo JS,Wang Z,Zhang L,Yu J

doi

10.1158/0008-5472.CAN-09-1996

subject

Has Abstract

pub_date

2009-10-15 00:00:00

pages

8157-65

issue

20

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-09-1996

journal_volume

69

pub_type

杂志文章

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