Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
J Endocrinol. 2020 Jul;246(1):13-27. doi: 10.1530/JOE-20-0055.
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.
慢性暴露于饱和脂肪酸（棕榈酸或硬脂酸）是导致胰岛素分泌受损的主要原因。然而，硬脂酸诱导的β细胞功能障碍的分子机制仍知之甚少。新出现的证据表明，miRNA 参与各种生物学功能。本研究旨在探讨与棕榈酸处理的β细胞相比，硬脂酸处理的β细胞中 miRNA 和 mRNA 的差异表达，并建立它们的共表达网络。β-TC-6 细胞用硬脂酸、棕榈酸或正常培养基处理 24 小时。通过高通量测序和生物信息学分析鉴定差异表达的 miRNA 和 mRNA。然后进行共表达网络、基因本体 (GO) 和通路分析。在β-TC-6 细胞和小鼠胰岛中验证选定的 miRNA 和 mRNA 的表达变化。测序分析检测到 656 个已知和 1729 个新的 miRNA。miRNA-mRNA 网络和 Venn 图分析显示，硬脂酸组中仅存在 2 个差异表达的 miRNA 和 63 个 mRNA。miR-374c-5p 的表达上调了 1.801log2（倍数变化），miR-297b-5p 的表达下调了 4.669log2（倍数变化）。我们发现 miR-297b-5p 和 miR-374c-5p 参与了硬脂酸诱导的β-TC-6 细胞脂毒性。此外，还验证了 miR-297b-5p 和 miR-374c-5p 对候选 mRNA 表达改变的影响。本研究表明，特定 miRNA 和 mRNA 的表达变化可能导致硬脂酸诱导的β细胞功能障碍，为进一步研究 2 型糖尿病发病过程中硬脂酸诱导的β细胞功能障碍的功能和分子机制提供了初步依据。
