MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells.

Details

Serval ID
serval:BIB_A030D87AF505
Type
Article: article from journal or magazin.
Publication sub-type
Editorial
Collection
Publications
Institution
Title
MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells.
Journal
Diabetes
Author(s)
Grieco F.A., Sebastiani G., Juan-Mateu J., Villate O., Marroqui L., Ladrière L., Tugay K., Regazzi R., Bugliani M., Marchetti P., Dotta F., Eizirik D.L.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
01/2017
Peer-reviewed
Oui
Volume
66
Number
1
Pages
100-112
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target genes remain to be clarified. We performed an miRNA expression profile on human islet preparations exposed to the cytokines IL-1β plus IFN-γ. Confirmation of miRNA and target gene modification in human β-cells was performed by real-time quantitative PCR. Single-stranded miRNAs inhibitors were used to block selected endogenous miRNAs. Cell death was measured by Hoechst/propidium iodide staining and activation of caspase-3. Fifty-seven miRNAs were detected as modulated by cytokines. Three of them, namely miR-23a-3p, miR-23b-3p, and miR-149-5p, were downregulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human β-cell apoptosis. These results identify a novel cross talk between a key family of miRNAs and proapoptotic Bcl-2 proteins in human pancreatic β-cells, broadening our understanding of cytokine-induced β-cell apoptosis in early T1D.
Keywords
Aged, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/metabolism, Blotting, Western, Female, Fluorescent Antibody Technique, HeLa Cells, Humans, Insulin-Secreting Cells/metabolism, Male, MicroRNAs/genetics, MicroRNAs/metabolism, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins/metabolism, RNA Interference
Pubmed
Web of science
Open Access
Yes
Create date
25/10/2016 18:13
Last modification date
20/08/2019 15:06
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