MicroRNA-181b suppresses TAG via target IRS2 and regulating multiple genes in the Hippo pathway

• Published in: Experimental cell research 2016-10, Vol.348 (1), p.66-74
• Main Authors: Chen, Zhi, Shi, HuaiPing, Sun, Shuang, Xu, HuiFen, Cao, DuoYao, Luo, Jun
• Format: Article
• Language: English
• Subjects: Adipocytes; Animals; Base Sequence; Epithelial Cells - metabolism; Fat metabolism; Fatty acids; Female; Gene Expression Regulation; Goats; Hippo pathway; Insulin Receptor Substrate Proteins - metabolism; IRS2; Lactation - genetics; Lipid Droplets - metabolism; Lipid Metabolism - genetics; Mammary Glands, Animal - cytology; Metabolism; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-181b; Models, Biological; Signal transduction; Signal Transduction - genetics; Transfection; Triglycerides - metabolism
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2016.09.004

Milk fat metabolism is a complex procedure controlled by several factors. MiRNAs (microRNAs) regulate expression of genes and influence a series of biological procedures, such as fatty acid metabolism. Here we screened expression of goat mammary gland's miRNA during peak-lactation and late-lactation, and found that miR-181b expresses remarkably. Moreover, we illustrated that the over-expression of miR-181b impaired fat metabolism while the knockdown of miR-181b promoted fat metabolism in GMEC. These findings extend the discovery of miR-181b functioning in mediating adipocyte differentiation, by suggesting its role in impairing fat metabolism, which develops our cognition on the importance of miRNAs in milk fat metabolism and synthesis. In this study, we find that over expressed miR-181b impaired adipogenesis and inhibited miR-181b promoted adipogenesis in GMEC. Using Luciferase reporter assay and Western Blot, IRS2 was illustrated to be a miR-181b’s potential target gene. What is interesting is that miR-181b regulates multiple key components in the Hippo pathway, such as LATS1 and YAP1 in GMECs. In conclusion, our findings indicated that miR-181b suppress fat metabolism by means of regulating multiple genes in the Hippo pathway and target IRS2, which promotes further study on the function of miRNAs in milk fat metabolism and synthesis. •After screening miRNAs in periods of peak-lactation and late-lactation, we have concluded that miR-181b shows a higher expression.•We established the regulating relation between miR-181b and its target gene IRS2, and conducted the rescue experiment to prove that miR-181b exercises its function indeed via IRS2.•We made a further research and discussion about the function of miR-181b and Wnt signaling pathway in the GMEC.