title: MiR-145 Regulates Lipogenesis in Goat Mammary Cells Via Targeting INSIG1 and Epigenetic Regulation of Lipid-Related Genes.
abstract: MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression at the post-transcriptional level to cause translational repression or degradation of targets. The profiles of miRNAs across stages of lactation in small ruminant species such as dairy goats is unknown. A small RNA library was constructed using tissue samples from mammary gland of Saanen dairy goats harvested at mid-lactation followed by sequencing via Solexa technology. A total of 796 conserved miRNAs, 263 new miRNAs, and 821 pre-miRNAs were uncovered. After comparative analyses of our sequence data with published mammary gland transcriptome data across different stages of lactation, a total of 37 miRNAs (including miR-145) had significant differences in expression over the lactation cycle. Further studies revealed that miR-145 regulates metabolism of fatty acids in goat mammary gland epithelial cells (GMEC). Compared with nonlactating mammary tissue, lactating mammary gland had a marked increase in expression of miR-145. Overexpression of miR-145 increased transcription of genes associated with milk fat synthesis resulting in greater fat droplet formation, triacylglycerol accumulation, and proportion of unsaturated fatty acids. In contrast, silencing of miR-145 impaired fatty acid synthesis. Inhibition of miR-145 increased methylation levels of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), peroxisome proliferator-activated receptor gamma (PPARG), and sterol regulatory element binding transcription factor 1 (SREBF1). Luciferase reporter assays confirmed that insulin induced gene 1 (INSIG1) is a direct target of miR-145. These findings underscore the need for further studies to evaluate the potential for targeting miR-145 for improving beneficial milk components in ruminant milk. J. Cell. Physiol. 232: 1030-1040, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: 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: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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: 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: 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: Yongqing
authors.initials: Y
authors.lastname: Yi
authors.affiliation: 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: Dawei
authors.initials: D
authors.lastname: Yao
authors.affiliation: 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: Xueying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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: Gongzhen
authors.initials: G
authors.lastname: Ma
authors.affiliation: Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, Illinois.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Loor
mesh_terms: D000818:Animals; D001483:Base Sequence; D033481:Chromosomes, Mammalian / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D006041:Goats / Q000235:genetics*; D007774:Lactation / Q000235:genetics; D008055:Lipids / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008055:Lipids; D008565:Membrane Proteins; D035683:MicroRNAs; D014157:Transcription Factors; D014280:Triglycerides