title: Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature.
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.
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Martin
authors.affiliation: Institute of Cytology, St-Petersburg, Russian Federation, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Anatskaya
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Erenpreisa
authors.affiliation: Systems Biology Institute, Seattle, USA.
authors.forename: Sui
authors.initials: S
authors.lastname: Huang
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Kristine
authors.initials: K
authors.lastname: Salmina
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Inna
authors.initials: I
authors.lastname: Inashkina
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Anda
authors.initials: A
authors.lastname: Huna
authors.affiliation: Institute of Cytology, St-Petersburg, Russian Federation, Russia.
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Nikolsky
authors.affiliation: Institute of Cytology, St-Petersburg, Russian Federation, Russia.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Vinogradov
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D004843:Epistasis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D055432:Metabolomics; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D011123:Polyploidy; D011247:Pregnancy; D060066:Protein Interaction Maps; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D016212:Transforming Growth Factor beta
keywords: EMT; Warburg; c-MYC interacting genes; polyploidy; stress