MiR-16a Regulates Milk Fat Metabolism by Targeting Large Tumor Suppressor Kinase 1 (LATS1) in Bovine Mammary Epithelial Cells

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作者
Chen, Zhi [1 ,2 ]
Chu, Shuangfeng [1 ,2 ]
Wang, Xiaolong [1 ,2 ]
Sun, Yujia [1 ,2 ]
Xu, Tianle [1 ,2 ]
Mao, Yongjiang [1 ,2 ]
Loor, Juan J. [3 ]
Yang, Zhangping [1 ,2 ]
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[1] College of Animal Science and Technology, Yangzhou University, Yangzhou,225009, China
[2] Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, Yangzhou,225009, China
[3] Mammalian Nutrition Physiology Genomics, Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana,IL,61801, United States
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Milk contains a number of beneficial fatty acids including short and medium chain and unsaturated conjugated and nonconjugated fatty acids. In this study; microRNA sequencing of mammary tissue collected in early-; peak-; mid-; and late-lactation periods was performed to determine the miRNA expression profiles. miR-16a was one of the differentially expressed miRNA and was selected for in-depth functional studies pertaining to fatty acid metabolism. The mimic of miR-16a impaired fat metabolism [triacylglycerol (TAG) and cholesterol] while knock-down of miR-16a promoted fat metabolism in vitro in bovine mammary epithelial cells (BMECs). In addition; the in vitro work with BMECs also revealed that miR-16a had a negative effect on the cellular concentration of cis 9-C18:1; total C18:1; C20:1; and C22:1 and long-chain polyunsaturated fatty acids. Therefore; these data suggesting a negative effect on fatty acid metabolism extend the discovery of the key role of miR-16a in mediating adipocyte differentiation. Through a combination of bioinformatics analysis; target gene 3′ UTR luciferase reporter assays; and western blotting; we identified large tumor suppressor kinase 1 (LATS1) as a target of miR-16a. Transfection of siRNA-LATS1 into BMECs led to increases in TAG; cholesterol; and cellular fatty acid concentrations; suggesting a positive role of LATS1 in mammary cell fatty acid metabolism. In summary; data suggest that miR-16a regulates biological processes associated with intracellular TAG; and unsaturated fatty acid synthesis through LATS1. These data provide a theoretical and experimental framework for further clarifying the regulation of lipid metabolism in mammary cells of dairy cows. © 2019 American Chemical Society;
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页码:11167 / 11178
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