Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer
Mueller S, Raulefs S, Bruns P, Afonso-Grunz F, Ploetner A, Thermann R, Jaeger C, Schlitter AM, Kong B, Regel I, Roth WK, Rotter B, Hoffmeier K, Kahl G, Koch I, Theis FJ, Kleeff J, Winter P, Michalski CW (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 14
Article Number: 94
Journal Issue: 1
DOI: 10.1186/s12943-015-0358-5
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.
Involved external institutions
Goethe-Universität Frankfurt am Main
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
GenXPro GmbH
Germany (DE)
GFE Gesellschaft zur Forschung, Entwicklung und Distribution von Diagnostika im Blutspendewesen mbH
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
GenXPro GmbH
Germany (DE)
GFE Gesellschaft zur Forschung, Entwicklung und Distribution von Diagnostika im Blutspendewesen mbH
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
How to cite
APA:
Mueller, S., Raulefs, S., Bruns, P., Afonso-Grunz, F., Ploetner, A., Thermann, R.,... Michalski, C.W. (2015). Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Molecular Cancer, 14(1). https://dx.doi.org/10.1186/s12943-015-0358-5
MLA:
Mueller, Soren, et al. "Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer." Molecular Cancer 14.1 (2015).
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