Oncotarget

Research Papers:

Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature

Alejandro Vazquez-Martin, Olga V. Anatskaya _, Alessandro Giuliani, Jekaterina Erenpreisa, Sui Huang, Kristine Salmina, Inna Inashkina, Anda Huna, Nikolai N. Nikolsky and Alexander E. Vinogradov

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Oncotarget. 2016; 7:75235-75260. https://doi.org/10.18632/oncotarget.12118

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Abstract

Alejandro Vazquez-Martin1,*, Olga V. Anatskaya2,*, Alessandro Giuliani3, Jekaterina Erenpreisa1,**, Sui Huang4, Kristine Salmina1, Inna Inashkina1, Anda Huna1, Nikolai N. Nikolsky2, Alexander E. Vinogradov2,**

1Latvian Biomedical Research and Study Centre, Riga, Latvia

2Institute of Cytology, St-Petersburg, Russian Federation, Russia

3Istituto Superiore di Sanità, Rome, Italy

4Systems Biology Institute, Seattle, USA

*Equal contribution

**Senior authors

Correspondence to:

Olga V. Anatskaya, email: olga.anatskaya@gmail.com

Keywords: c-MYC interacting genes, polyploidy, Warburg, stress, EMT

Received: June 03, 2016     Accepted: September 05, 2016     Published: September 19, 2016

ABSTRACT

The dependence of cancer on overexpressed c-MYC and its predisposition for polyploidy represents a double puzzle. We address this conundrum by cross-species transcription analysis of c-MYC interacting genes in polyploid vs. diploid tissues and cells, including human vs. mouse heart, mouse vs. human liver and purified 4n vs. 2n mouse decidua cells. Gene-by-gene transcriptome comparison and principal component analysis indicated that c-MYC interactants are significantly overrepresented among ploidy-associated genes. Protein interaction networks and gene module analysis revealed that the most upregulated genes relate to growth, stress response, proliferation, stemness and unicellularity, as well as to the pathways of cancer supported by MAPK and RAS coordinated pathways. A surprising feature was the up-regulation of epithelial-mesenchymal transition (EMT) modules embodied by the N-cadherin pathway and EMT regulators from SNAIL and TWIST families. Metabolic pathway analysis also revealed the EMT-linked features, such as global proteome remodeling, oxidative stress, DNA repair and Warburg-like energy metabolism. Genes associated with apoptosis, immunity, energy demand and tumour suppression were mostly down-regulated. Noteworthy, despite the association between polyploidy and ample features of cancer, polyploidy does not trigger it. Possibly it occurs because normal polyploidy does not go that far in embryonalisation and linked genome destabilisation. In general, the analysis of polyploid transcriptome explained the evolutionary relation of c-MYC and polyploidy to cancer.


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