Karagiannopoulos Alexandros, Esguerra Jonathan L S, Pedersen Morten G, Wendt Anna, Prasad Rashmi B, Eliasson Lena
Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences-Malmö, Lund University, CRC 91-11, Box 50332, 202 13 Malmö, Sweden.
Clinical Research Centre, Skåne University Hospital, CRC 91-11, Box 50332, 202 13 Malmö, Sweden.
iScience. 2022 Feb 26;25(4):103995. doi: 10.1016/j.isci.2022.103995. eCollection 2022 Apr 15.
MicroRNAs (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, -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.
微小RNA（miRNA）是一类短的非编码RNA，通过靶向mRNA来调节基因表达，在胰岛中发挥重要作用。我们旨在确定与血糖状态导致的miRNA表达改变相关的分子途径和基因组调控区域，这可能有助于2型糖尿病（T2D）的发展。为此，通过对血糖水平正常和升高的供体的人胰岛样本进行差异miRNA表达和相关性分析相结合的方法来鉴定miRNA。对这些miRNA的高度相关、经过实验验证的基因靶标进行分析和聚类，揭示了两个胰岛特异性簇，它们与胰岛功能的关键方面相关，并且包含大量与T2D相关的基因。最后，通过整合表达定量性状位点（eQTL）和公共全基因组关联研究（GWAS）数据，发现了与胰岛素分泌和T2D相关的潜在基因组信号。本研究中提出的基于miRNA驱动网络的方法有助于更好地理解T2D发病机制中胰岛素分泌受损的情况。
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