Human Pancreatic Islet MiRNA-mRNA Networks of Altered MiRNAs Due to Glycemic Status

Overview

Journal iScience

Publisher Cell Press

Date 2022 Mar 21

PMID 35310942

Authors

Alexandros Karagiannopoulos

Jonathan L S Esguerra

Morten G Pedersen

Anna Wendt

Rashmi B Prasad

Lena Eliasson

Affiliations

Soon will be listed here.

Abstract

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.

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