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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.

SUBMITTER: Okamoto K 

PROVIDER: S-EPMC3321205 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver.

Okamoto Koji K   Ishiguro Tatsuya T   Midorikawa Yutaka Y   Ohata Hirokazu H   Izumiya Masashi M   Tsuchiya Naoto N   Sato Ai A   Sakai Hiroaki H   Nakagama Hitoshi H  

The EMBO journal 20120228 7


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 li  ...[more]

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