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miR-146a-5p inhibits TNF-alpha-induced adipogenesis via targeting insulin receptor in primary porcine adipocytes

文献类型： 外文期刊

作者： Wu, Di 1 ; Xi, Qian-Yun 1 ; Cheng, Xiao 1 ; Dong, Tao 1 ; Zhu, Xiao-Tong 1 ; Shu, Gang 2 ; Wang, Li-Na; Jiang, Qing-Ya 1 ;

作者机构： 1.South China Agr Univ, Coll Anim Sci, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Natl Engn Res Ctr Swine Breeding Ind, Guangzhou 510642, Guangdong, Peoples R China

2.South China Agr Univ, Coll Anim Sci, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Natl Engn Res Ctr Swine Breeding Ind, Guangzhou 510642, Guangdong, Peoples R

关键词： microarray;pig model;Gene Ontology;insulin receptor substrate-1;microRNA

期刊名称：JOURNAL OF LIPID RESEARCH （ 影响因子：5.922； 五年影响因子：6.203 ）

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收录情况： SCI

摘要： TNF-alpha is a multifunctional cytokine participating in immune disorders, inflammation, and tumor development with regulatory effects on energy metabolism. Our work focused on the function of TNF-alpha in adipogenesis of primary porcine adipocytes. TNF-alpha could suppress the insulin receptor (IR) at the mRNA and protein levels. Microarray analysis of TNF-alpha-treated porcine adipocytes was used to screen out 29 differentially expressed microRNAs (miRNAs), 13 of which were remarkably upregulated and 16 were intensely downregulated. These 29 differentially expressed miRNAs were predicted to mainly participate in the insulin signaling pathway, adipocytokine signaling pathway, and type 2 diabetes mellitus pathway by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. miR-146a-5p, reportedly involved in immunity and cancer relevant processes, was one of the most highly differentially expressed miRNAs after TNF-alpha treatment. Red Oil O staining and TG assay revealed that miR-146a-5p suppressed adipogenesis. A dual-luciferase reporter and siRNA assay verified that miR-146a-5p targeted IR and could inhibit its protein expression. miR-146a-5p was also validated to be involved in the insulin signaling pathway by reducing tyrosine phosphorylation of insulin receptor substrate-1.(jr) Our study provides the first evidence of miR-146a-5p targeting IR, which facilitates future studies related to obesity and diabetes using pig models.-Wu, D., Q-Y. Xi, X. Cheng, T. Dong, X-T. Zhu, G. Shu, L-N. Wang, Q-Y. Jiang, and Y-L. Zhang. miR-146a-5p inhibits TNF-alpha-induced adipogenesis via targeting insulin receptor in primary porcine adipocytes.

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