Cellular and Molecular Life Sciences

, Volume 69, Issue 12, pp 2041–2055 | Cite as

Identification of putative cancer genes through data integration and comparative genomics between plants and humans

  • Mauricio Quimbaya
  • Klaas Vandepoele
  • Eric Raspé
  • Michiel Matthijs
  • Stijn Dhondt
  • Gerrit T. S. Beemster
  • Geert Berx
  • Lieven De Veylder
Research Article

Abstract

Coordination of cell division with growth and development is essential for the survival of organisms. Mistakes made during replication of genetic material can result in cell death, growth defects, or cancer. Because of the essential role of the molecular machinery that controls DNA replication and mitosis during development, its high degree of conservation among organisms is not surprising. Mammalian cell cycle genes have orthologues in plants, and vice versa. However, besides the many known and characterized proliferation genes, still undiscovered regulatory genes are expected to exist with conserved functions in plants and humans. Starting from genome-wide Arabidopsis thaliana microarray data, an integrative strategy based on coexpression, functional enrichment analysis, and cis-regulatory element annotation was combined with a comparative genomics approach between plants and humans to detect conserved cell cycle genes involved in DNA replication and/or DNA repair. With this systemic strategy, a set of 339 genes was identified as potentially conserved proliferation genes. Experimental analysis confirmed that 20 out of 40 selected genes had an impact on plant cell proliferation; likewise, an evolutionarily conserved role in cell division was corroborated for two human orthologues. Moreover, association analysis integrating Homo sapiens gene expression data with clinical information revealed that, for 45 genes, altered transcript levels and relapse risk clearly correlated. Our results illustrate how a systematic exploration of the A. thaliana genome can contribute to the experimental identification of new cell cycle regulators that might represent novel oncogenes or/and tumor suppressors.

Keywords

Arabidopsis thaliana MCF7 Cell cycle Cancer genomics Comparative genomics 

Abbreviations

CDK

Cyclin-dependent kinase

EI

Endoreduplication index

fRMA

Frozen Robust Multiarray Analysis

GO

Gene ontology

HU

Hydroxyurea

PCC

Pearson correlation coefficient

PWM

Positional Weight Matrix

QPCR

Quantitative polymerase chain reaction

siRNA

Small interfering RNA

Notes

Acknowledgments

We thank all members of the cell cycle and oncology groups for fruitful discussions and suggestions, the Arabidopsis Biological Research Center for providing the T-DNA insertion lines, and Martine De Cock and Lorena López for help in preparing the manuscript. This work was supported by grants from the Interuniversity Poles of Attraction Programne (IUAP VI/33), initiated by the Belgian State, Science Policy Office, the Research Foundation-Flanders (grant no. G008306), Ghent University (“Geconcerteerde Onderzoeksacties” no.01G013B7), the Stichting tegen Kanker (no. 189-2008), the Association for International Cancer Research (Scotland), the EU-FP6 framework program BRECOSM LSHC-CT-2004-503224, and the EU-FP7 framework program TuMIC 2008-201662. M.Q. is indebted with the VIB international PhD program. K.V. acknowledges the support by Ghent University (Multidisciplinary Research Partnership “Bioinformatics: from nucleotides to networks”) and the Interuniversity Attraction Poles Programme (IUAP P6/25), initiated by the Belgian State, Science Policy Office (BioMaGNet). S.D. is indebted to the Agency for Innovation through Science and Technology for a predoctoral fellowship.

Supplementary material

18_2011_909_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1852 kb)
18_2011_909_MOESM2_ESM.docx (26 kb)
Supplementary material 2 (DOCX 26 kb)
18_2011_909_MOESM3_ESM.xls (1.4 mb)
Supplementary material 3 (XLS 1,452 kb)

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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Mauricio Quimbaya
    • 1
    • 2
    • 3
    • 4
  • Klaas Vandepoele
    • 1
    • 2
  • Eric Raspé
    • 3
    • 4
  • Michiel Matthijs
    • 1
    • 2
  • Stijn Dhondt
    • 1
    • 2
  • Gerrit T. S. Beemster
    • 1
    • 2
    • 5
  • Geert Berx
    • 3
    • 4
  • Lieven De Veylder
    • 1
    • 2
  1. 1.Department of Plant Systems BiologyVIBGentBelgium
  2. 2.Department of Plant Biotechnology and BioinformaticsGhent UniversityGentBelgium
  3. 3.Molecular and Cellular Oncology Unit, Department for Molecular Biomedical ResearchVIBGentBelgium
  4. 4.Department of Biomedical Molecular BiologyGhent UniversityGentBelgium
  5. 5.Department of BiologyUniversity of AntwerpAntwerpenBelgium

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