期刊
EMBO JOURNAL
卷 31, 期 7, 页码 1752-1763出版社
WILEY
DOI: 10.1038/emboj.2012.25
关键词
colon cancer; IGF-1R; metastasis; miR-493
资金
- Ministry of Health, Labor and Welfare
- National Institute of Biomedical Innovation (NiBio)
- Foundation for Promotion of Cancer Research (FPCR, Japan)
- Grants-in-Aid for Scientific Research [23300359] Funding Source: KAKEN
Liver metastasis is a major lethal complication associated with colon cancer, and post-intravasation steps of the metastasis are important for its clinical intervention. In order to identify inhibitory microRNAs (miRNAs) for these steps, we performed 'dropout' screens of a miRNA library in a mouse model of liver metastasis. Functional analyses showed that miR-493 and to a lesser extent miR-493* were capable of inhibiting liver metastasis. miR-493 inhibited retention of metastasized cells in liver parenchyma and induced their cell death. IGF1R was identified as a direct target of miR-493, and its inhibition partially phenocopied the anti-metastatic effects. High levels of miR-493 and miR-493*, but not pri-miR-493, in primary colon cancer were inversely related to the presence of liver metastasis, and attributed to an increase of miR-493 expression during carcinogenesis. We propose that, in a subset of colon cancer, upregulation of miR-493 during carcinogenesis prevents liver metastasis via the induction of cell death of metastasized cells. The EMBO Journal (2012) 31, 1752-1763. doi: 10.1038/emboj.2012.25; Published online 28 February 2012
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据