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miR‐493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver
Author(s) -
Okamoto Koji,
Ishiguro Tatsuya,
Midorikawa Yutaka,
Ohata Hirokazu,
Izumiya Masashi,
Tsuchiya Naoto,
Sato Ai,
Sakai Hiroaki,
Nakagama Hitoshi
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.25
Subject(s) - cancer , library science , medicine , computer science
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.