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Genes Nutr. 2015 Sep;10(5):35. doi: 10.1007/s12263-015-0484-0. Epub 2015 Aug 15.

Integrative network-based analysis of mRNA and microRNA expression in 1,25-dihydroxyvitamin D3-treated cancer cells.

Genes & nutrition

Martina Kutmon, Susan L Coort, Kim de Nooijer, Claire Lemmens, Chris T Evelo

Affiliations

  1. Department of Bioinformatics - BiGCaT, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
  2. Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.

PMID: 26276506 PMCID: PMC4537452 DOI: 10.1007/s12263-015-0484-0

Abstract

Nutritional systems biology is an evolving research field aimed at understanding nutritional processes at a systems level. It is known that the development of cancer can be influenced by the nutritional status, and the link between vitamin D status and different cancer types is widely investigated. In this study, we performed an integrative network-based analysis using a publicly available data set studying the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in prostate cancer cells on mRNA and microRNA level. Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways. The changes in the G1-to-S cell cycle pathway showed that 1,25(OH)2D3 down-regulates the genes influencing the G1-to-S phase transition. Moreover, after 1,25(OH)2D3 treatment the gene expression in several cancer-related processes was down-regulated. The more general pathways were merged into one network and then extended with known protein-protein and transcription factor-gene interactions. Network algorithms were used to (1) identify active network modules and (2) integrate microRNA regulation in the network. Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH)2D3 treatment. Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN, an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5, a receptor for Wnt proteins that was up-regulated. The extendable network-based tools PathVisio and Cytoscape enable straightforward, in-depth and integrative analysis of mRNA and microRNA expression data in 1,25(OH)2D3-treated cancer cells.

References

  1. Carcinogenesis. 2012 Jul;33(7):1319-26 - PubMed
  2. Bioinformatics. 2009 Apr 15;25(8):1091-3 - PubMed
  3. Mol Cell. 2007 Jul 6;27(1):91-105 - PubMed
  4. J Biol Chem. 2003 Nov 21;278(47):46862-8 - PubMed
  5. Clin Cancer Res. 2003 Mar;9(3):1077-82 - PubMed
  6. Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15 - PubMed
  7. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):411-5 - PubMed
  8. Prostate. 2004 May 15;59(3):243-51 - PubMed
  9. Eur Rev Med Pharmacol Sci. 2011 May;15(5):469-80 - PubMed
  10. Adv Exp Med Biol. 2014;810:33-51 - PubMed
  11. Biochim Biophys Acta. 2014 Nov;1843(11):2365-75 - PubMed
  12. F1000Res. 2014 Jul 01;3:148 - PubMed
  13. Nucleic Acids Res. 2012 Jan;40(Database issue):D1301-7 - PubMed
  14. Mol Endocrinol. 2005 Nov;19(11):2685-95 - PubMed
  15. J Integr Bioinform. 2014 Mar 28;11(1):235 - PubMed
  16. F1000Res. 2014 Jul 01;3:152 - PubMed
  17. Mol Cancer. 2011 May 18;10:58 - PubMed
  18. Nature. 2012 Sep 6;489(7414):91-100 - PubMed
  19. Methods Enzymol. 2006;411:352-69 - PubMed
  20. BMC Genomics. 2010 Jan 13;11:26 - PubMed
  21. Curr Opin Clin Nutr Metab Care. 2009 May;12(3):223-6 - PubMed
  22. Genome Res. 2003 Nov;13(11):2498-504 - PubMed
  23. Mol Nutr Food Res. 2014 Feb;58(2):343-52 - PubMed
  24. Nucleic Acids Res. 2014 Jan;42(Database issue):D78-85 - PubMed
  25. PLoS One. 2013 Dec 05;8(12):e82160 - PubMed
  26. PLoS One. 2012;7(11):e49029 - PubMed
  27. PLoS Comput Biol. 2015 Feb 23;11(2):e1004085 - PubMed
  28. Bioinformatics. 2002;18 Suppl 1:S233-40 - PubMed
  29. J Steroid Biochem Mol Biol. 2004 Oct;92(3):131-41 - PubMed

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