文章基本信息

标题：Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
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作者：Alexandros Karagiannopoulos ; Jonathan L.S. Esguerra ; Morten G. Pedersen 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-17
DOI：10.1016/j.isci.2022.103995
语种：English
出版社：Elsevier
摘要：SummaryMicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression via mRNA targeting, playing important roles in the pancreatic islets. We aimed to identify molecular pathways and genomic regulatory regions associated with altered miRNA expression due to glycemic status, which could contribute to the development of type 2 diabetes (T2D). To this end, miRNAs were identified by a combination of differential miRNA expression and correlation analysis in human islet samples from donors with normal and elevated blood glucose levels. Analysis and clustering of highly correlated, experimentally validated gene targets of these miRNAs revealed two islet-specific clusters, which were associated with key aspects of islet functions and included a high number of T2D-related genes. Finally,cis-eQTLs and public GWAS data integration uncovered suggestive genomic signals of association with insulin secretion and T2D. The miRNA-driven network-based approach presented in this study contributes to a better understanding of impaired insulin secretion in T2D pathogenesis.Graphical abstractDisplay OmittedHighlights•Network-based islet miRNA approaches provide a better insight into T2D pathogenesis•Islets from healthy and hyperglycemic donors have distinct miRNA profiles•Differentially expressed miRNAs regulate gene networks that affect islet function•Specific miRNA eQTLs overlap with insulin secretion and T2D genetic markersEndocrinology; Omics