First Author | Hasseine LK | Year | 2009 |
Journal | Biochem Biophys Res Commun | Volume | 390 |
Issue | 4 | Pages | 1278-82 |
PubMed ID | 19883627 | Mgi Jnum | J:155599 |
Mgi Id | MGI:4414867 | Doi | 10.1016/j.bbrc.2009.10.135 |
Citation | Hasseine LK, et al. (2009) miR-139 impacts FoxO1 action by decreasing FoxO1 protein in mouse hepatocytes. Biochem Biophys Res Commun 390(4):1278-82 |
abstractText | 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. |