Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status

Summary: 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 coul...

Full description

Bibliographic Details
Main Authors: Alexandros Karagiannopoulos, Jonathan L.S. Esguerra, Morten G. Pedersen, Anna Wendt, Rashmi B. Prasad, Lena Eliasson
Format: Article
Language:English
Published: Elsevier 2022-04-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222002656
_version_ 1818287621915279360
author Alexandros Karagiannopoulos
Jonathan L.S. Esguerra
Morten G. Pedersen
Anna Wendt
Rashmi B. Prasad
Lena Eliasson
author_facet Alexandros Karagiannopoulos
Jonathan L.S. Esguerra
Morten G. Pedersen
Anna Wendt
Rashmi B. Prasad
Lena Eliasson
author_sort Alexandros Karagiannopoulos
collection DOAJ
description Summary: 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, 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.
first_indexed 2024-12-13T01:43:24Z
format Article
id doaj.art-ba747488ce9947c39be22282e5dfc512
institution Directory Open Access Journal
issn 2589-0042
language English
last_indexed 2024-12-13T01:43:24Z
publishDate 2022-04-01
publisher Elsevier
record_format Article
series iScience
spelling doaj.art-ba747488ce9947c39be22282e5dfc5122022-12-22T00:03:42ZengElsevieriScience2589-00422022-04-01254103995Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic statusAlexandros Karagiannopoulos0Jonathan L.S. Esguerra1Morten G. Pedersen2Anna Wendt3Rashmi B. Prasad4Lena Eliasson5Islet 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, SwedenIslet 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, SwedenDepartment of Information Engineering, University of Padova, Padua, ItalyIslet 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, SwedenClinical Research Centre, Skåne University Hospital, CRC 91-11, Box 50332, 202 13 Malmö, Sweden; Genomics, Diabetes and Endocrinology, Lund University Diabetes Centre Department of Clinical Sciences-Malmö, Lund University, Malmö, SwedenIslet 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; Corresponding authorSummary: 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, 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.http://www.sciencedirect.com/science/article/pii/S2589004222002656EndocrinologyOmics
spellingShingle Alexandros Karagiannopoulos
Jonathan L.S. Esguerra
Morten G. Pedersen
Anna Wendt
Rashmi B. Prasad
Lena Eliasson
Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
iScience
Endocrinology
Omics
title Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
title_full Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
title_fullStr Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
title_full_unstemmed Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
title_short Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
title_sort human pancreatic islet mirna mrna networks of altered mirnas due to glycemic status
topic Endocrinology
Omics
url http://www.sciencedirect.com/science/article/pii/S2589004222002656
work_keys_str_mv AT alexandroskaragiannopoulos humanpancreaticisletmirnamrnanetworksofalteredmirnasduetoglycemicstatus
AT jonathanlsesguerra humanpancreaticisletmirnamrnanetworksofalteredmirnasduetoglycemicstatus
AT mortengpedersen humanpancreaticisletmirnamrnanetworksofalteredmirnasduetoglycemicstatus
AT annawendt humanpancreaticisletmirnamrnanetworksofalteredmirnasduetoglycemicstatus
AT rashmibprasad humanpancreaticisletmirnamrnanetworksofalteredmirnasduetoglycemicstatus
AT lenaeliasson humanpancreaticisletmirnamrnanetworksofalteredmirnasduetoglycemicstatus