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Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes
Published on: September 9, 2021
miR-139 impacts FoxO1 action by decreasing FoxO1 protein in mouse hepatocytes
Larbi Kamal Hasseine1, Charlotte Hinault, Patricia Lebrun
1INSERM U907, Nice F-06107, France.
Abstract:
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.
Insights
MicroRNAs fine-tune gene expression. Researchers found that miR-139 directly targets FoxO1 mRNA, reducing FoxO1 protein levels and impacting its target genes in mouse hepatocytes.
Area of Science:
- Molecular Biology
- Gene Regulation
- Hepatocyte Function
Background:
- Forkhead box protein O1 (FoxO1) is a critical regulator of cellular signaling pathways influenced by growth factors and hormones like insulin.
- FoxO1 activity is modulated by its subcellular localization and post-translational modifications, including phosphorylation, ubiquitination, and acetylation.
- MicroRNAs (miRNAs) represent a newly discovered mechanism for cells to precisely control gene expression.
Purpose of the Study:
- To investigate the potential role of microRNAs in regulating FoxO1.
- To identify specific miRNAs that target FoxO1 in liver cells.
- To elucidate the functional consequences of miRNA-mediated FoxO1 regulation.
Main Methods:
- Utilized immortalized neonatal mouse hepatocytes for experimental analysis.
- Employed techniques to assess miRNA targeting of FoxO1 mRNA.
- Quantified changes in FoxO1 protein and mRNA levels.
- Measured the expression of FoxO1 target genes (AdQR1, AdQR2, Mttp).
Main Results:
- Identified miR-139 as a direct targeting miRNA for FoxO1 mRNA.
- Observed a reduction in FoxO1 protein levels upon miR-139 activity, with no significant change in mRNA levels.
- Demonstrated a subsequent decrease in the expression of FoxO1 target genes, including AdQR1, AdQR2, and Mttp.
- Showcased miR-139's role in modulating FoxO1 protein homeostasis.
Conclusions:
- Established a novel regulatory mechanism for FoxO1 involving miR-139.
- Suggests that miR-139 contributes to maintaining FoxO1 protein levels for homeostatic regulation of its transcriptional activity.
- Highlights the importance of miRNA-mediated regulation in response to environmental stimuli.