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Plate IV.506 · Publications

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

Article in Molecular Cancer, 25 April 2015.

Open accessmiRNA, Target, Cancer

  1. Sören Müller
  2. Susanne Raulefs
  3. Philipp Bruns
  4. Fabian Afonso-Grunz
  5. Anne Plötner
  6. Rolf Thermann
  7. Carsten Jäger
  8. Anna Melissa Schlitter
  9. Bo Kong
  10. Ivonne Regel
  11. W Kurt Roth
  12. Björn Rotter
  13. Klaus Hoffmeier
  14. Günter Kahl
  15. Ina Koch
  16. Fabian J Theis
  17. Jörg Kleeff
  18. Peter Winter
  19. Christoph W Michalski

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.

Versions2

  1. CorrectionMolecular Cancer10.1186/s12943-015-0401-6
  2. PublishedMolecular Cancer10.1186/s12943-015-0358-5

Cite

@article{muller2015next,
  title = {{Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer}},
  author = {Müller, Sören and Raulefs, Susanne and Bruns, Philipp and Afonso-Grunz, Fabian and Plötner, Anne and Thermann, Rolf and Jäger, Carsten and Schlitter, Anna Melissa and Kong, Bo and Regel, Ivonne and Roth, W Kurt and Rotter, Björn and Hoffmeier, Klaus and Kahl, Günter and Koch, Ina and Theis, Fabian J and Kleeff, Jörg and Winter, Peter and Michalski, Christoph W},
  journal = {Molecular Cancer},
  publisher = {Springer Science and Business Media LLC},
  year = {2015},
  month = apr,
  doi = {10.1186/s12943-015-0358-5},
  url = {https://doi.org/10.1186/s12943-015-0358-5},
  pmid = {25910082},
  pmcid = {PMC4417536}
}
.bib file