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| Status |
Public on May 21, 2020 |
| Title |
Arsenic is more potent than cadmium or manganese in disrupting the INS-1 beta cell microRNA landscape |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Diabetes is a metabolic disorder characterized by fasting hyperglycemia and impaired glucose tolerance. Laboratory and population studies have shown that inorganic arsenic (iAs) can impair these pathways. Other metals including cadmium (Cd) and manganese (Mn) have also been linked to diabetes phenotypes. MicroRNAs, short non-coding RNAs that regulate gene expression, have emerged as potential drivers of metabolic dysfunction. MicroRNAs responsive to metal exposures in vitro have also been reported in independent studies to regulate insulin secretion in vivo. We hypothesize that microRNA dysregulation may associate with and possibly contribute to insulin secretion impairment upon exposure to iAs, Cd, or Mn. We exposed insulin secreting rat insulinoma cells to non-cytotoxic concentrations of iAs (1 µM), Cd (5 µM), and Mn (25 µM) for 24 h followed by small RNA sequencing to identify dysregulated microRNAs. RNA sequencing was then performed to further investigate changes in gene expression caused by iAs exposure. While all three metals significantly inhibited glucose-stimulated insulin secretion, high-throughput sequencing revealed distinct microRNA profiles specific to each exposure. One of the most significantly upregulated microRNAs post-iAs treatment is miR-146a (~ + 2-fold), which is known to be activated by nuclear factor κB (NF-κB) signaling. Accordingly, we found by RNA-seq analysis that genes upregulated by iAs exposure are enriched in the NF-κB signaling pathway and genes down-regulated by iAs exposure are enriched in miR-146a binding sites and are involved in regulating beta cell function. Notably, iAs exposure caused a significant decrease in the expression of Camk2a, a calcium-dependent protein kinase that regulates insulin secretion, has been implicated in type 2 diabetes, and is a likely target of miR-146a. Further studies are needed to elucidate potential interactions among NF-kB, miR-146a, and Camk2a in the context of iAs exposure.
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| Overall design |
Exposure of rat insulinoma cells to iAs, Cd, or Mn followed by small RNA sequencing (iAs, Cd, & Mn) or RNA sequencing (iAs)
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| Contributor(s) |
Sethupathy P, Beck R, Kanke M |
| Citation(s) |
31555879 |
| Submission date |
May 21, 2019 |
| Last update date |
Aug 20, 2020 |
| Contact name |
Praveen Sethupathy |
| Organization name |
Cornell University
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| Lab |
Dr. Sethupathy Lab
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| Street address |
Cornell University College of Veterinary Medicine, Box 17
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| City |
Ithica |
| State/province |
NY |
| ZIP/Postal code |
14853 |
| Country |
USA |
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| Platforms (2) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
| GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA543993 |
| SRA |
SRP199047 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE131544_DESeq2_normalized_counts.csv.gz |
1.1 Mb |
(ftp)(http) |
CSV |
| GSE131544_miRquant_RPMMM.csv.gz |
31.4 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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