The role of long non-coding RNAs in the regulation of pancreatic beta cell identity

TY - JOUR

T1 - The role of long non-coding RNAs in the regulation of pancreatic beta cell identity

AU - Wilson, Maya E.

AU - Pullen, Timothy J.

N1 - Funding Information: This work was supported by the joint King’s College London and Technische Universität Dresden IRTG programme and by Diabetes UK (grant number 19/0006062). Publisher Copyright: © 2021 Portland Press Ltd. All rights reserved.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Type 2 diabetes (T2D) is a widespread disease affecting millions in every continental population. Pancreatic β-cells are central to the regulation of circulating glucose, but failure in the maintenance of their mass and/or functional identity leads to T2D. Long non-coding RNAs (lncRNAs) represent a relatively understudied class of transcripts which growing evidence implicates in diabetes pathogenesis. T2D-associated single nucleotide polymorphisms (SNPs) have been identified in lncRNA loci, although these appear to function primarily through regulating β-cell proliferation. In the last decade, over 1100 lncRNAs have been catalogued in islets and the roles of a few have been further investigated, definitively linking them to β-cell function. These studies show that lncRNAs can be developmentally regulated and show highly tissue-specific expression. lncRNAs regulate neighbouring β-cell-specific transcription factor expression, with knockdown or overexpression of lncRNAs impacting a network of other key genes and pathways. Finally, gene expression analysis in studies of diabetic models have uncovered a number of lncRNAs with roles in β-cell function. A deeper understanding of these lncRNA roles in maintaining β-cell identity, and its deterioration, is required to fully appreciate the β-cell molecular network and to advance novel diabetes treatments.

AB - Type 2 diabetes (T2D) is a widespread disease affecting millions in every continental population. Pancreatic β-cells are central to the regulation of circulating glucose, but failure in the maintenance of their mass and/or functional identity leads to T2D. Long non-coding RNAs (lncRNAs) represent a relatively understudied class of transcripts which growing evidence implicates in diabetes pathogenesis. T2D-associated single nucleotide polymorphisms (SNPs) have been identified in lncRNA loci, although these appear to function primarily through regulating β-cell proliferation. In the last decade, over 1100 lncRNAs have been catalogued in islets and the roles of a few have been further investigated, definitively linking them to β-cell function. These studies show that lncRNAs can be developmentally regulated and show highly tissue-specific expression. lncRNAs regulate neighbouring β-cell-specific transcription factor expression, with knockdown or overexpression of lncRNAs impacting a network of other key genes and pathways. Finally, gene expression analysis in studies of diabetic models have uncovered a number of lncRNAs with roles in β-cell function. A deeper understanding of these lncRNA roles in maintaining β-cell identity, and its deterioration, is required to fully appreciate the β-cell molecular network and to advance novel diabetes treatments.

UR - http://www.scopus.com/inward/record.url?scp=85118415738&partnerID=8YFLogxK

U2 - 10.1042/BST20210207

DO - 10.1042/BST20210207

M3 - Article

C2 - 34581756

AN - SCOPUS:85118415738

SN - 0300-5127

VL - 49

SP - 2153

EP - 2161

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

IS - 5

ER -