title: miR-148a and miR-17-5p synergistically regulate milk TAG synthesis via PPARGC1A and PPARA in goat mammary epithelial cells.
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.
authors.affiliation: a Shaanxi Key Laboratory of Molecular Biology for Agriculture , College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a Shaanxi Key Laboratory of Molecular Biology for Agriculture , College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: a Shaanxi Key Laboratory of Molecular Biology for Agriculture , College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Sun
authors.affiliation: a Shaanxi Key Laboratory of Molecular Biology for Agriculture , College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , P.R. China.
authors.forename: Duoyao
authors.initials: D
authors.lastname: Cao
authors.affiliation: a Shaanxi Key Laboratory of Molecular Biology for Agriculture , College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , P.R. China.
authors.forename: Huaiping
authors.initials: H
authors.lastname: Shi
authors.affiliation: b Mammalian Nutrition Physiology Genomics, Department of Animal Sciences and Division of Nutritional Sciences , University of Illinois , Urbana , IL , USA.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Loor
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D020029:Base Pairing; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006041:Goats; D059014:High-Throughput Nucleotide Sequencing; D050356:Lipid Metabolism / Q000235:genetics; D008321:Mammary Glands, Animal / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008892:Milk / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger
keywords: PPARA; PPARGC1A; miR-148a; miR-17–5p; triacylglycerol synthesis