Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood

Shahnaz Haque; Ryan M. Ames; Karen Moore; Benjamin P. Lee; Nicola Jeffery; Lorna W. Harries

doi:10.1186/s12920-020-0713-2

BMC Medical Genomics (Apr 2020)

Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood

Shahnaz Haque,
Ryan M. Ames,
Karen Moore,
Benjamin P. Lee,
Nicola Jeffery,
Lorna W. Harries

Affiliations

Shahnaz Haque: RNA-Mediated Mechanisms of Disease Group, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter
Ryan M. Ames: Biosciences, University of Exeter
Karen Moore: College of Life and Environmental Sciences, University of Exeter
Benjamin P. Lee: RNA-Mediated Mechanisms of Disease Group, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter
Nicola Jeffery: RNA-Mediated Mechanisms of Disease Group, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter
Lorna W. Harries: RNA-Mediated Mechanisms of Disease Group, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter

DOI: https://doi.org/10.1186/s12920-020-0713-2
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 15

Abstract

Read online

Abstract Background Circular RNAs are non-coding RNA molecules with gene regulatory potential that have been associated with several human diseases. They are stable and present in the circulation, making them excellent candidates for biomarkers of disease. Despite their promise as biomarkers or future therapeutic targets, information on their expression and functionality in human pancreatic islets is a relatively unexplored subject. Methods Here we aimed to produce an enriched circRNAome profile for human pancreatic islets by CircleSeq, and to explore the relationship between circRNA expression, diabetes status, genotype at T2D risk loci and measures of glycaemia (insulin secretory index; SI and HbA1c) in human islet preparations from healthy control donors and donors with type 2 diabetes using ANOVA or linear regression as appropriate. We also assessed the effect of elevated glucose, cytokine and lipid and hypoxia on circRNA expression in the human beta cell line EndoC-βH1. Results We identified over 2600 circRNAs present in human islets. Of the five most abundant circRNAs in human islets, four (circCIRBP, circZKSCAN, circRPH3AL and circCAMSAP1) demonstrated marked associations with diabetes status. CircCIRBP demonstrated an association with insulin secretory index in isolated human islets and circCIRBP and circRPH3AL displayed altered expression with elevated fatty acid in treated EndoC-βH1 cells. CircCAMSAP1 was also noted to be associated with T2D status in human peripheral blood. No associations between circRNA expression and genotype at T2D risk loci were identified in our samples. Conclusions Our data suggest that circRNAs are abundantly expressed in human islets, and that some are differentially regulated in the islets of donors with type 2 diabetes. Some islet circRNAs are also expressed in peripheral blood and the expression of one, circCAMSAP1, correlates with diabetes status. These findings highlight the potential of circRNAs as biomarkers for T2D.

Published in BMC Medical Genomics

ISSN: 1755-8794 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine; Science: Biology (General): Genetics
Website: https://bmcmedgenomics.biomedcentral.com

About the journal

Abstract

Keywords