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

Peng Wang, Fangdong Zou, Zhang Xiaodong, Li Hua, Austin Dulak, Robert J. Tomko, John S. Lazo, Wang Zhenghe, Zhang Lin, Yu Jian

Research output: Contribution to journalArticlepeer-review

279 Scopus citations

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 G1-S transition, and participates in DNA damage-induced G2-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.

Original languageEnglish
Pages (from-to)8157-8165
Number of pages9
JournalCancer Research
Volume69
Issue number20
DOIs
StatePublished - 15 Oct 2009
Externally publishedYes

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