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

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


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.

MeSH terms

  • Apoptosis
  • Bromodeoxyuridine
  • Cell Cycle*
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • DNA Damage
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Luciferases / metabolism
  • MicroRNAs / physiology*
  • Mitotic Index
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • cdc25 Phosphatases


  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • Luciferases
  • CDC25A protein, human
  • cdc25 Phosphatases
  • Bromodeoxyuridine