24. Circulating microRNAs as Biomarkers of Drug-Induced Pancreatitis

  1. Saura C. Sahu
  1. Rodney L. Rouse,
  2. Barry A. Rosenzweig and
  3. Karol L. Thompson

Published Online: 6 SEP 2013

DOI: 10.1002/9781118695999.ch24

microRNAs in Toxicology and Medicine

microRNAs in Toxicology and Medicine

How to Cite

Rouse, R. L., Rosenzweig, B. A. and Thompson, K. L. (2013) Circulating microRNAs as Biomarkers of Drug-Induced Pancreatitis, in microRNAs in Toxicology and Medicine (ed S. C. Sahu), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9781118695999.ch24

Editor Information

  1. Division of Toxicology, Center for Food Safety and Applied Nutrition, Food and Drug Administration, USA

Author Information

  1. Division of Drug Safety Research, Center for Drug Evaluation and Research, US Food and Drug Administration, USA

Publication History

  1. Published Online: 6 SEP 2013
  2. Published Print: 7 OCT 2013

ISBN Information

Print ISBN: 9781118401613

Online ISBN: 9781118695999

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Keywords:

  • microRNA;
  • biomarker;
  • serum;
  • pancreatitis;
  • pancreas;
  • miR216a;
  • miR217

Summary

MicroRNAs are a novel source of potential biomarkers of drug-induced toxicity. These short, noncoding RNAs can exhibit tissue-selective patterns of expression and are present in biofluids in a form that is protected from ribonuclease digestion. Tissue injury and other pathologies can lead to the release of microRNAs into circulation. There is special interest in the potential use of microRNAs as biomarkers of pathologies that currently lack sensitive or specific biomarkers. Drug-induced pancreatitis is difficult to accurately diagnose because it produces nonspecific symptoms and the clinical biomarkers commonly used to diagnose acute pancreatitis, serum amylase and lipase, have limited sensitivity and specificity. Two microRNAs that are enriched in pancreas (miR216a and miR217) may be of potential use as serum biomarkers of drug-induced pancreatitis. Using highly sensitive reverse transcription quantitative polymerase chain reaction assays, the response of serum miR-216a and miR-217 was evaluated in an experimental model of acute pancreatitis induced in male C57BL6 mice by caerulein, a cholecystokinin analog. Serum levels of miR-216a and miR-217 increased in proportion to the severity of caerulein-induced injury to pancreatic acinar cells and decreased with reversal of injury. The injury-induced time course and dose response of pancreas-selective microRNAs was similar to serum amylase. Caerulein treatment had only minor effects on serum levels of miR-16, a microRNA that is not selective for pancreas. These results suggest that circulating levels of exocrine pancreas-enriched microRNAs have potential value as highly specific biomarkers of acute pancreatic injury.