Human pancreatic islet miRNA-mRNA networks of altered miRNAs due to glycemic status
Alexandros Karagiannopoulos,
Jonathan L.S. Esguerra,
Morten G. Pedersen,
Anna Wendt,
Rashmi B. Prasad,
Lena Eliasson
Affiliations
Alexandros Karagiannopoulos
Islet 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
Jonathan L.S. Esguerra
Islet 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
Morten G. Pedersen
Department of Information Engineering, University of Padova, Padua, Italy
Anna Wendt
Islet 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
Rashmi B. Prasad
Clinical 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, Sweden
Lena Eliasson
Islet 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 author
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.
