Oncogenomics

Oncogene (2007) 26, 4442–4452; doi:10.1038/sj.onc.1210228; published online 22 January 2007

MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma

A E Szafranska1, T S Davison1, J John1, T Cannon1, B Sipos2, A Maghnouj3, E Labourier1,4 and S A Hahn3,4

  1. 1Asuragen Inc., Austin, Woodward, TX, USA
  2. 2Department of Pathology, University of Kiel, Kiel, Germany
  3. 3Department of Internal Medicine, Knappschaftskrankenhaus, University of Bochum, Bochum, Germany

Correspondence: Dr S Hahn, Department of Internal Medicine, Ruhr-University Bochum, Molecular GI-Oncology (MGO), Zentrum fuer klinische Forschung (ZKF), Universitaetsstras zlige 150, Bochum 44780, Germany. E-mail: stephan.hahn@rub.de; Dr E Labourier, Asuragen, Inc., 2150 Woodward, Austin TX 78744, USA. E-mail: elabourier@asuragen.com

4These authors contributed equally to this work and should be considered joint senior authors.

Received 21 September 2006; Revised 14 November 2006; Accepted 17 November 2006; Published online 22 January 2007.

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is known for its very poor overall prognosis. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. We used 377 feature microRNA (miRNA) arrays to investigate miRNA expression in normal pancreas, chronic pancreatitis, and PDAC tissues as well as PDAC-derived cell lines. A pancreatic miRNome was established comparing the data from normal pancreas with a reference set of 33 human tissues. The expression of miR-216 and -217 and lack of expression of miR-133a were identified as characteristic of pancreas tissue. Unsupervised clustering showed that the three pancreatic tissues types can be classified according to their respective miRNA expression profiles. We identified 26 miRNAs most prominently misregulated in PDAC and a relative quantitative reverse transcriptase-polymerase chain reaction index using only miR-217 and -196a was found to discriminate normal pancreas, chronic pancreatitis and cancerous tissues, establishing a potential utility for miRNAs in diagnostic procedures. Lastly, comparing differentially expressed genes from PDAC with predicted miRNA target genes for the top 26 miRNAs, we identified potential novel links between aberrant miRNA expression and known target genes relevant to PDAC biology. Our data provides novel insights into the miRNA-driven pathophysiological mechanisms involved in PDAC development and offers new candidate targets to be exploited both for diagnostic and therapeutic strategies.

Keywords:

pancreatic ductal adenocarcinoma, chronic pancreatitis, microRNA, expression profiling

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