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Series GSE255756 Query DataSets for GSE255756
Status Public on Apr 10, 2024
Title miR-146a-5p contributes to inflammation-mediated β cell mitochondrial dysfunction and apoptosis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary MicroRNAs (miRNAs) are small non-coding RNAs that function as modulators of gene expression. We previously showed that miR-146a-5p is upregulated in pancreatic islets treated with pro-inflammatory cytokines and in pancreatic sections from organ donors with type 1 diabetes (T1D). Other studies have associated overexpression of miR-146a-5p with β cell apoptosis and impaired insulin secretion; however, the molecular mechanisms mediating these effects remain elusive. To investigate the role of miR-146a-5p in β cell function, we developed stable MIN6 cell lines transduced with lentiviral vectors to either overexpress or inhibit the expression of miR-146a-5p. Monoclonal cell populations were treated with pro-inflammatory cytokines (IL1β, IFNg, and TNFα) to model T1D in vitro. We found that overexpression of miR-146a-5p increased the cell death of MIN6 cells under inflammatory stress, whereas inhibition of miR-146a-5p reversed these effects. Additionally, inhibition of miR-146a-5p increased mitochondrial DNA copy number, respiration rate, and ATP production, suggesting that miR-146a-5p inhibition improves mitochondrial function. In support of this finding, we also observed that miR-146a-5p is enriched in the mitochondria of MIN6 cells treated with cytokines. Consistently, bioinformatic analysis of RNA sequencing data using MIN6 stable cells showed enrichment of pathways related to insulin secretion, apoptosis, and mitochondrial function when the expression levels of miR-146a-5p were altered. Overall, the findings from our study show for the first time that miR-146a-5p upregulation during inflammatory stress may promote β cell dysfunction and death by suppressing mitochondrial function.
 
Overall design We developed MIN6 stable cells using lentiviral vectors to overexpress / inhibit miR-146a-5p. MIN6 cells transduced with scrambled sequence was used as the control. mRNA sequencing was performed on MIN6 cells treated with and without proinflammatory cytokines and differentially expressed genes were identified by comparing different pairs.
 
Contributor(s) Evans-Molina C, Krishnan P, Syed F
Citation(s) 38562689
Submission date Feb 14, 2024
Last update date Apr 10, 2024
Contact name Carmella Evans-Molina
E-mail(s) cevansmo@iupui.edu
Organization name Indiana University School of Medicine
Street address MS2059 Barnhill Drive
City Indianapolis
State/province Indiana
ZIP/Postal code 46202
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (24)
GSM8078982 MIN6 stable cells overexpressing miR-146a-5p treated with proinflammatory cytokines - replicate1 [P65-OE-Cy]
GSM8078983 MIN6 stable cells overexpressing miR-146a-5p without proinflammatory cytokines - replicate1 [P65-OE]
GSM8078984 Control MIN6 stable cells transduced with scrambled treated with proinflammatory cytokines - replicate1 [P65-SCR-Cy]
Relations
BioProject PRJNA1076462

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Supplementary file Size Download File type/resource
GSE255756_Normalized_counts.txt.gz 1.6 Mb (ftp)(http) TXT
GSE255756_Rawcounts.txt.gz 1.2 Mb (ftp)(http) TXT
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