| First Author | Okamoto K | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 7 | Pages | 1752-63 |
| PubMed ID | 22373578 | Mgi Jnum | J:182694 |
| Mgi Id | MGI:5316339 | Doi | 10.1038/emboj.2012.25 |
| Citation | Okamoto K, et al. (2012) miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver. EMBO J 31(7):1752-63 |
| abstractText | 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. |
