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Mol Cancer. 2015 Apr 25;14:94. doi: 10.1186/s12943-015-0358-5.

Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer.

Author information

1
Molecular BioSciences, Goethe University, Frankfurt am Main, Germany. s.mueller@bio.uni-frankfurt.de.
2
GenXPro GmbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. s.mueller@bio.uni-frankfurt.de.
3
Molecular Bioinformatics Group, Institute of Computer Science, Cluster of Excellence Frankfurt 'Macromolecular Complexes' Faculty of Computer Science and Mathematics, Frankfurt am Main, Germany. s.mueller@bio.uni-frankfurt.de.
4
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. susanne.raulefs@tum.de.
5
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. philipp.bruns@helmholtz-muenchen.de.
6
Molecular BioSciences, Goethe University, Frankfurt am Main, Germany. fgrunz@stud.uni-frankfurt.de.
7
GenXPro GmbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. fgrunz@stud.uni-frankfurt.de.
8
GenXPro GmbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. ploetner@genxpro.de.
9
GFE Blut mbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. rolf.thermann@gfeblut.de.
10
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. Carsten.Jaeger@lrz.tu-muenchen.de.
11
Department of Pathology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. melissa.schlitter@lrz.tu-muenchen.de.
12
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. kongbo81@hotmail.com.
13
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. ivonne.regel@lrz.tum.de.
14
GFE Blut mbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. kurt.roth@gfeblut.de.
15
GenXPro GmbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. rotter@genxpro.de.
16
GenXPro GmbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. hoffmeier@genxpro.de.
17
Molecular BioSciences, Goethe University, Frankfurt am Main, Germany. kahl@em.uni-frankfurt.de.
18
Molecular Bioinformatics Group, Institute of Computer Science, Cluster of Excellence Frankfurt 'Macromolecular Complexes' Faculty of Computer Science and Mathematics, Frankfurt am Main, Germany. ina.koch@bioinformatik.uni-frankfurt.de.
19
Institute of Computational Biology, Helmholtz Zentrum Munich, Neuherberg, Germany. fabian.theis@helmholtz-muenchen.de.
20
Department of Mathematics, TU Munich, Boltzmannstrasse 3, Garching, Germany. fabian.theis@helmholtz-muenchen.de.
21
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. kleeff@tum.de.
22
GenXPro GmbH, Frankfurt Biotechnology Innovation Center, Frankfurt am Main, Germany. pwinter@genxpro.de.
23
Department of Surgery, University of Heidelberg, Heidelberg, Germany. cwmichalski@gmail.com.

Abstract

BACKGROUND:

Previous studies identified microRNAs (miRNAs) and messenger RNAs with significantly different expression between normal pancreas and pancreatic cancer (PDAC) tissues. Due to technological limitations of microarrays and real-time PCR systems these studies focused on a fixed set of targets. Expression of other RNA classes such as long intergenic non-coding RNAs or sno-derived RNAs has rarely been examined in pancreatic cancer. Here, we analysed the coding and non-coding transcriptome of six PDAC and five control tissues using next-generation sequencing.

RESULTS:

Besides the confirmation of several deregulated mRNAs and miRNAs, miRNAs without previous implication in PDAC were detected: miR-802, miR-2114 or miR-561. SnoRNA-derived RNAs (e.g. sno-HBII-296B) and piR-017061, a piwi-interacting RNA, were found to be differentially expressed between PDAC and control tissues. In silico target analysis of miR-802 revealed potential binding sites in the 3' UTR of TCF4, encoding a transcription factor that controls Wnt signalling genes. Overexpression of miR-802 in MiaPaCa pancreatic cancer cells reduced TCF4 protein levels. Using Massive Analysis of cDNA Ends (MACE) we identified differential expression of 43 lincRNAs, long intergenic non-coding RNAs, e.g. LINC00261 and LINC00152 as well as several natural antisense transcripts like HNF1A-AS1 and AFAP1-AS1. Differential expression was confirmed by qPCR on the mRNA/miRNA/lincRNA level and by immunohistochemistry on the protein level.

CONCLUSIONS:

Here, we report a novel lncRNA, sncRNA and mRNA signature of PDAC. In silico prediction of ncRNA targets allowed for assigning potential functions to differentially regulated RNAs.

PMID:
25910082
PMCID:
PMC4417536
DOI:
10.1186/s12943-015-0358-5
[Indexed for MEDLINE]
Free PMC Article

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