miR-30e-5p and miR-15a Synergistically Regulate Fatty Acid Metabolism in Goat Mammary Epithelial Cells via LRP6 and YAP1

Int J Mol Sci. 2016 Nov 16;17(11):1909. doi: 10.3390/ijms17111909.

Abstract

MicroRNA (miRNA) regulates the expression of genes and influences a series of biological processes, including fatty acid metabolism. We screened the expression of miRNA in goat mammary glands during peak-lactation and non-lactating ("dry") periods, and performed an in vitro study with goat mammary epithelial cells (GMEC) prior to sequencing analysis. Results illustrated that miR-30e-5p and miR-15a were highly expressed. Utilizing a luciferase reporter assay and Western blot, low-density lipoprotein receptor-related protein 6 (LRP6) and Yes associated protein 1 (YAP1) genes were demonstrated to be a target of miR-30e-5p and miR-15a in GMEC. Moreover, we demonstrated that the overexpression of miR-30e-5p and miR-15a in GMEC promoted fat metabolism while their knockdown impaired fat metabolism. These findings extend the discovery of a key role of miR-30e-5p and miR-15a in mediating adipocyte differentiation by suggesting a role in promoting milk fat synthesis. In conclusion, our findings indicate that miR-30e-5p, together with miR-15a, represses expression of LRP6 and promotes fat metabolism in GMEC. The data expanded our knowledge on the function of miRNAs in milk fat metabolism and synthesis in ruminant mammary cells.

Keywords: LRP6; YAP1; fat metabolism; miR-15a; miR-30e-5p.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Epithelial Cells / metabolism
  • Fatty Acids / genetics
  • Fatty Acids / metabolism*
  • Female
  • Gene Expression Regulation*
  • Goats / genetics*
  • Goats / metabolism
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-6 / genetics*
  • Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • Fatty Acids
  • Low Density Lipoprotein Receptor-Related Protein-6
  • MicroRNAs