Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer

Cell Cycle. 2008 Aug 15;7(16):2591-600. doi: 10.4161/cc.7.16.6533. Epub 2008 Aug 1.


Recently, we and others identified the microRNA miR-34a as a target of the tumor suppressor gene product p53. Ectopic miR-34a induces a G(1) cell cycle arrest, senescence and apoptosis. Here we report that miR-34a expression is silenced in several types of cancer due to aberrant CpG methylation of its promoter. 19 out of 24 (79.1%) primary prostate carcinomas displayed CpG methylation of the miR-34a promoter and concomitant loss of miR-34a expression. CpG methylation of the miR-34a promoter was also detected in breast (6/24; 25%), lung (7/24; 29.1%), colon (3/23; 13%), kidney (3/14; 21.4%), bladder (2/6; 33.3%) and pancreatic (3/19; 15.7%) carcinoma cell lines, as well as in melanoma cell lines (19/44; 43.2%) and primary melanoma (20/32 samples; 62.5%). Silencing of miR-34a was dominant over its transactivation by p53 after DNA damage. Re-expression of miR-34a in prostate and pancreas carcinoma cell lines induced senescence and cell cycle arrest at least in part by targeting CDK6. These results show that miR-34a represents a tumor suppressor gene which is inactivated by CpG methylation and subsequent transcriptional silencing in a broad range of tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • CpG Islands*
  • Cyclin-Dependent Kinase 6 / metabolism
  • DNA Methylation*
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasms / genetics*
  • Promoter Regions, Genetic
  • Tumor Suppressor Protein p53 / metabolism


  • MIRN34 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase 6