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miR-22 represses cancer progression by inducing cellular senescence

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 impa...

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Detalles Bibliográficos
Autores principales: Xu, Dan, Takeshita, Fumitaka, Hino, Yumiko, Fukunaga, Saori, Kudo, Yasusei, Tamaki, Aya, Matsunaga, Junko, Takahashi, Ryou-u, Takata, Takashi, Shimamoto, Akira, Ochiya, Takahiro, Tahara, Hidetoshi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080260/
https://www.ncbi.nlm.nih.gov/pubmed/21502362
http://dx.doi.org/10.1083/jcb.201010100
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author Xu, Dan
Takeshita, Fumitaka
Hino, Yumiko
Fukunaga, Saori
Kudo, Yasusei
Tamaki, Aya
Matsunaga, Junko
Takahashi, Ryou-u
Takata, Takashi
Shimamoto, Akira
Ochiya, Takahiro
Tahara, Hidetoshi
author_facet Xu, Dan
Takeshita, Fumitaka
Hino, Yumiko
Fukunaga, Saori
Kudo, Yasusei
Tamaki, Aya
Matsunaga, Junko
Takahashi, Ryou-u
Takata, Takashi
Shimamoto, Akira
Ochiya, Takahiro
Tahara, Hidetoshi
author_sort Xu, Dan
collection PubMed
description 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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spelling pubmed-30802602011-10-18 miR-22 represses cancer progression by inducing cellular senescence Xu, Dan Takeshita, Fumitaka Hino, Yumiko Fukunaga, Saori Kudo, Yasusei Tamaki, Aya Matsunaga, Junko Takahashi, Ryou-u Takata, Takashi Shimamoto, Akira Ochiya, Takahiro Tahara, Hidetoshi J Cell Biol Research Articles 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. The Rockefeller University Press 2011-04-18 /pmc/articles/PMC3080260/ /pubmed/21502362 http://dx.doi.org/10.1083/jcb.201010100 Text en © 2011 Xu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Xu, Dan
Takeshita, Fumitaka
Hino, Yumiko
Fukunaga, Saori
Kudo, Yasusei
Tamaki, Aya
Matsunaga, Junko
Takahashi, Ryou-u
Takata, Takashi
Shimamoto, Akira
Ochiya, Takahiro
Tahara, Hidetoshi
miR-22 represses cancer progression by inducing cellular senescence
title miR-22 represses cancer progression by inducing cellular senescence
title_full miR-22 represses cancer progression by inducing cellular senescence
title_fullStr miR-22 represses cancer progression by inducing cellular senescence
title_full_unstemmed miR-22 represses cancer progression by inducing cellular senescence
title_short miR-22 represses cancer progression by inducing cellular senescence
title_sort mir-22 represses cancer progression by inducing cellular senescence
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080260/
https://www.ncbi.nlm.nih.gov/pubmed/21502362
http://dx.doi.org/10.1083/jcb.201010100
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