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Biochem Biophys Res Commun. 2009 Dec 25;390(4):1278-82. doi: 10.1016/j.bbrc.2009.10.135. Epub 2009 Oct 31.

miR-139 impacts FoxO1 action by decreasing FoxO1 protein in mouse hepatocytes.

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  • 1INSERM U907, Nice F-06107, France.


FoxO1 is a master regulator of signaling pathways used by growth factors and hormones, including insulin. Its activity is regulated by changes in subcellular localization coupled to post-translational modifications such as phosphorylation, ubiquitination, and acetylation. As microRNAs have emerged as a newly identified means by which cells fine-tune gene expression, we hypothesized that they could regulate FoxO1. Since FoxO1 plays a key role in the liver, we used immortalized neonatal mouse hepatocytes to analyze the effects of potential microRNAs targeting FoxO1. We found that miR-139 targets FoxO1 mRNA directly and reduces the level of the protein without affecting transcript levels. This decrease in FoxO1 protein results in a decrease of its target genes, such as AdQR1, AdQR2 and Mttp. Our findings suggest a novel mode of FoxO1 regulation by which miR-139 could maintain the protein level of FoxO1 to preserve homeostatic regulation of its transcriptional activity in response to environmental stimuli.

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