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

miR-22 represses cancer progression by inducing cellular senescence.

Author information

1
Department of Cellular and Molecular Biology, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan.

Abstract

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.

PMID:
21502362
PMCID:
PMC3080260
DOI:
10.1083/jcb.201010100
[Indexed for MEDLINE]
Free PMC Article

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