title: miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver.
abstract: 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.
authors.affiliation: Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo, Japan. kojokamo@ncc.go.jo
authors.forename: Koji
authors.initials: K
authors.lastname: Okamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ishiguro
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Midorikawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohata
authors.forename: Masashi
authors.initials: M
authors.lastname: Izumiya
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Ai
authors.initials: A
authors.lastname: Sato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology*; D005480:Flurbiprofen / Q000031:analogs & derivatives; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C555448:MIRN493 microRNA, human; D035683:MicroRNAs; C095631:nitroflurbiprofen; D005480:Flurbiprofen; D017526:Receptor, IGF Type 1