miRNA-mRNA profile and regulatory network in stearic acid-treated β-cell dysfunction

in Journal of Endocrinology
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  • 1 Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China
  • 2 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

Correspondence should be addressed to H Lu or C Sun: lhm_519@sina.com or changhaosun2002@163.com
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Chronic exposure of pancreatic β-cells to saturated fatty acid (palmitic or stearic acid) is a leading cause of impaired insulin secretion. However, the molecular mechanisms underlying stearic-acid-induced β-cell dysfunction remain poorly understood. Emerging evidence indicates that miRNAs are involved in various biological functions. The aim of this study was to explore the differential expression of miRNAs and mRNAs, specifically in stearic-acid-treated- relative to palmitic-acid-treated β-cells, and to establish their co-expression networks. β-TC-6 cells were treated with stearic acid, palmitic acid or normal medium for 24 h. Differentially expressed miRNAs and mRNAs were identified by high-throughput sequencing and bioinformatic analysis. Co-expression network, gene ontology (GO) and pathway analyses were then conducted. Changes in the expression of selected miRNAs and mRNAs were verified in β-TC-6 cells and mouse islets. Sequencing analysis detected 656 known and 1729 novel miRNAs. miRNA-mRNA network and Venn-diagram analysis yielded two differentially expressed miRNAs and 63 mRNAs exclusively in the stearic-acid group. miR-374c-5p was up-regulated by a 1.801 log2(fold-change) and miR-297b-5p was down-regulated by a −4.669 log2(fold-change). We found that miR-297b-5p and miR-374c-5p were involved in stearic-acid-induced lipotoxicity to β-TC-6 cells. Moreover, the effects of miR-297b-5p and miR-374c-5p on the alterations of candidate mRNAs expressions were verified. This study indicates that expression changes of specific miRNAs and mRNAs may contribute to stearic-acid-induced β-cell dysfunction, which provides a preliminary basis for further functional and molecular mechanism studies of stearic-acid-induced β-cell dysfunction in the development of type 2 diabetes.

Supplementary Materials

    • Supplementary Table 1 The composition of the diet for mice
    • Supplementary Table 2 The differentially expressed miRNA in palmitic acid-induced β-TC 6 cells compared both with stearic acid and control group.
    • Supplementary Table 3 The differentially expressed miRNAs both in stearic and palmitic acid-induced β-TC 6 cells compared with control group.
    • Supplementary Table 4 The log2FoldChange of differentially expressed mRNAs in stearic acid-induced β-TC 6 cells compared both with palmitic acid and control group.
    • Supplementary Table 5 The log2FoldChange of differentially expressed mRNAs in palmitic acid-induced β-TC 6 cells compared both with stearic acid and control group.
    • Supplementary Table 6 The top 10 up- and down-regulated differentially expressed mRNAs both in stearic and palmitic acid-induced β-TC 6 cells compared with control group.
    • Supplementary Table 7 The composition of fasting serum NEFAs profile in normal and HSD mice at 16 weeks
    • Supplementary Table 8 Body weight and serum analysis in normal and HSD mice at 16 weeks.

 

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