miR-22 represses cancer progression by inducing cellular senescence

J Cell Biol. 2011 Apr 18;193(2):409-24. doi: 10.1083/jcb.201010100.


Cellular senescence acts as a barrier to cancer progression, and microRNAs (miRNAs) are thought to be potential senescence regulators. However, whether senescence-associated miRNAs (SA-miRNAs) contribute to tumor suppression remains unknown. Here, we report that miR-22, a novel SA-miRNA, has an impact on tumorigenesis. miR-22 is up-regulated in human senescent fibroblasts and epithelial cells but down-regulated in various cancer cell lines. miR-22 overexpression induces growth suppression and acquisition of a senescent phenotype in human normal and cancer cells. miR-22 knockdown in presenescent fibroblasts decreased cell size, and cells became more compact. miR-22-induced senescence also decreases cell motility and inhibits cell invasion in vitro. Synthetic miR-22 delivery suppresses tumor growth and metastasis in vivo by inducing cellular senescence in a mouse model of breast carcinoma. We confirmed that CDK6, SIRT1, and Sp1, genes involved in the senescence program, are direct targets of miR-22. Our study provides the first evidence that miR-22 restores the cellular senescence program in cancer cells and acts as a tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cellular Senescence / genetics*
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism
  • Down-Regulation
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation


  • MIRN22 microRNA, human
  • MicroRNAs
  • Sp1 Transcription Factor
  • Tumor Suppressor Protein p53
  • Cdk6 protein, mouse
  • Cyclin-Dependent Kinase 6
  • Sirt1 protein, mouse
  • Sirtuin 1