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      1. Author :
        Xu, D.; Takeshita, F.; Hino, Y.; Fukunaga, S.; Kudo, Y.; Tamaki, A.; Matsunaga, J.; Takahashi, R. U.; Takata, T.; Shimamoto, A.; Ochiya, T.; Tahara, H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
      5. Publication :
        J Cell Biol
      6. Products :
      7. Volume :
      8. Issue :
      9. Page Numbers :
      10. Research Area :
      11. Keywords :
        MDA-MB-231-D3H2Ln, IVIS, Bioluminescence
      12. 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.
      13. URL :
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
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