Possible role of miR-2909 RNomics in arsenic mediated pancreatic β-cell dysfunction

J Trace Elem Med Biol. 2018 Dec;50:263-267. doi: 10.1016/j.jtemb.2018.07.006. Epub 2018 Jul 10.

Abstract

Chronic exposure of humans to inorganic arsenic as a potential risk for the incidence of diabetes has received wide attention. However, the biological mechanism through which arsenic plays a role in the development of diabetes is still being evaluated. One of the hallmark of diabetes is the β-cell dysfunction followed by the changes in the insulin secretion. Pancreatic duodenal homeobox 1 (PDX1) has been widely recognized to play crucial role in the β-cell development, survival and its regulation of insulin gene expression. Many of the arsenic mediated cellular affects have been shown to be regulated by miR-2909 in vitro. Our present study provides evidence to reveal that arsenic affects miR-2909 expression in the pancreatic β-cell and this novel miRNA regulates PDX1 transcriptional expression indirectly through genes coding for c-Jun, MafA, PI3K and directly at the translational level by targeting the PDX1 mRNA. We provide further evidence for this miR-2909 RNomics in pancreatic tissue obtained from NOD mice where the expression of miR-2909 was high compared to the control mice. Keeping in view the fact that arsenic is known to cause β-cell dysfunction and most of the cellular effects of arsenic have been shown to be mediated through miR-2909 RNomics, our study revealed that arsenic employs miR-2909 (at low doses) and c-Jun (at high doses) to down regulate PDX1 in order to cause β-cell dysfunction leading to diabetic state.

Keywords: Arsenic; Hyperglycemia; PDX1; miR-2909 RNomics; β-cells.

MeSH terms

  • Animals
  • Arsenic / pharmacology*
  • Cell Line, Tumor
  • Homeodomain Proteins / metabolism
  • Insulin-Secreting Cells
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Trans-Activators / metabolism

Substances

  • Homeodomain Proteins
  • MIRN2909 microRNA, human
  • MicroRNAs
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Arsenic