miR-148a and miR-17–5p synergistically regulate milk TAG synthesis via PPARGC1A and PPARA in goat mammary epithelial cells

Zhi Chen, Jun Luo, Shuang Sun, Duoyao Cao, Huaiping Shi, Juan J. Loor

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNA (miRNA) are a class of ‘18–25’ nt RNA molecules which regulate gene expression and play an important role in several biologic processes including fatty acid metabolism. Here we used S-Poly (T) and high-throughput sequencing to evaluate the expression of miRNA and mRNA during early-lactation and in the non-lactating (“dry”) period in goat mammary gland tissue. Results indicated that miR-148a, miR-17–5p, PPARGC1A and PPARA are highly expressed in the goat mammary gland in early-lactation and non-lactating periods. Utilizing a Luciferase reporter assay and Western Blot, PPARA, an important regulator of fatty acid oxidation, and PGC1a (PPARGC1A), a major regulator of fat metabolism, were demonstrated to be targets of miR-148a and miR-17–5p in goat mammary epithelial cells (GMECs). It was also revealed that miR-148a expression can regulate PPARA, and miR-17–5p represses PPARGC1A in GMECs. Furthermore, the overexpression of miR-148a and miR-17–5p promoted triacylglycerol (TAG) synthesis while the knockdown of miR-148a and miR-17–5p impaired TAG synthesis in GMEC. These findings underscore the importance of miR-148a and miR-17–5p as key components in the regulation of TAG synthesis. In addition, miR-148a cooperates with miR-17–5p to regulate fatty acid metabolism by repressing PPARGC1A and PPARA in GMECs. Further studies on the functional role of miRNAs in lipid metabolism of ruminant mammary cells seem warranted.

Original languageEnglish (US)
Pages (from-to)326-338
Number of pages13
JournalRNA Biology
Volume14
Issue number3
DOIs
StatePublished - Mar 4 2017

Keywords

  • PPARA
  • PPARGC1A
  • miR-148a
  • miR-17–5p
  • triacylglycerol synthesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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