miR-22 represses cancer progression by inducing cellular senescence.
miR-22 represses cancer progression by inducing cellular senescence.
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DOI：
10.1083/jcb.201010100
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发表时间：
2011-04-18
期刊：
影响因子：
--
通讯作者：
Tahara H
中科院分区：
文献类型：
--
作者：
Xu D;Takeshita F;Hino Y;Fukunaga S;Kudo Y;Tamaki A;Matsunaga J;Takahashi RU;Takata T;Shimamoto A;Ochiya T;Tahara H
microRNA miR-22靶向CDK 6、SIRT 1和Sp1--参与衰老程序调控的基因--以抑制细胞生长和增殖。细胞衰老是癌症进展的障碍，而microRNAs（miRNAs）被认为是潜在的衰老调节因子。然而，衰老相关的miRNAs（SA-miRNAs）是否有助于肿瘤抑制仍然未知。在这里，我们报告了一种新的SA-miRNA miR-22对肿瘤发生的影响。miR-22在人衰老成纤维细胞和上皮细胞中上调，但在各种癌细胞系中下调。miR-22过表达诱导人正常细胞和癌细胞的生长抑制和衰老表型的获得。衰老成纤维细胞中的miR-22敲低降低了细胞大小，并且细胞变得更加紧凑。miR-22诱导的衰老还降低细胞运动性并抑制体外细胞侵袭。合成miR-22递送通过在乳腺癌小鼠模型中诱导细胞衰老来抑制体内肿瘤生长和转移。我们证实了CDK 6、SIRT 1和Sp1这些参与衰老程序的基因是miR-22的直接靶点。我们的研究提供了第一个证据，证明miR-22恢复癌细胞的细胞衰老程序，并作为肿瘤抑制因子。
The microRNA miR-22 targets CDK6, SIRT1, and Sp1—genes involved in regulation of the senescence program—to suppress cell growth and proliferation. 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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影响因子：
2.6
作者：
Choong, Meng Ling;Yang, Henry He;McNiece, Ian
通讯作者：
McNiece, Ian
影响因子：
8
作者：
Belguise, K;Kersual, N;Chalbos, D
通讯作者：
Chalbos, D
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
2
作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
通讯作者：
Naoe, Tomoki
DOI：
10.1073/pnas.0707628104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Fabbri, Muller;Garzon, Ramiro;Croce, Carlo M.
通讯作者：
Croce, Carlo M.