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...
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Format: | Article |
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Elsevier
2022-04-01
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Series: | iScience |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222002656 |
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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 |
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