title: miR-22 represses cancer progression by inducing cellular senescence.
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.
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Takeshita
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hino
authors.forename: Saori
authors.initials: S
authors.lastname: Fukunaga
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.forename: Aya
authors.initials: A
authors.lastname: Tamaki
authors.forename: Junko
authors.initials: J
authors.lastname: Matsunaga
authors.forename: Ryou-U
authors.initials: RU
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.forename: Akira
authors.initials: A
authors.lastname: Shimamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1