期刊
JOURNAL OF CELL BIOLOGY
卷 193, 期 2, 页码 409-424出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201010100
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Japan Science and Technology Agency
- Takeda Science Foundation
- National Institute of Biomedical Innovation
- Grants-in-Aid for Scientific Research [23300363, 21115008, 23650626] Funding Source: KAKEN
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.
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