6533b86ffe1ef96bd12cd305

RESEARCH PRODUCT

Aneuploid IMR90 cells induced by depletion of pRB, DNMT1 and MAD2 show a common gene expression signature

Sergio SpataforaViviana BarraSalvatore FeoSerena BivonaDanilo CilluffoAldo Di LeonardoClaudia CoronnelloFlavia Contino

subject

DNA (Cytosine-5-)-Methyltransferase 1AneuploidyBiologyMicroarrayReal-Time Polymerase Chain ReactionRetinoblastoma ProteinCell LineRNA interferenceGene expressionProtein Interaction MappingGeneticsmedicineHumansGeneOligonucleotide Array Sequence AnalysisMicroarray analysis techniquesGene Expression ProfilingBioinformatics analysiChromosomeFibroblastsmedicine.diseaseAneuploidyGene Expression RegulationRNAiMad2 ProteinsDNMT1Cancer researchKIF4ARNA InterferenceTranscriptomeIMR90 human fibroblast

description

Chromosome segregation defects lead to aneuploidy which is a major feature of solid tumors. How diploid cells face chromosome mis-segregation and how aneuploidy is tolerated in tumor cells are not completely defined yet. Thus, an important goal of cancer genetics is to identify gene networks that underlie aneuploidy and are involved in its tolerance. To this aim, we induced aneuploidy in IMR90 human primary cells by depleting pRB, DNMT1 and MAD2 and analyzed their gene expression profiles by microarray analysis. Bioinformatic analysis revealed a common gene expression profile of IMR90 cells that became aneuploid. Gene Set Enrichment Analysis (GSEA) also revealed gene-sets/pathways that are shared by aneuploid IMR90 cells that may be exploited for novel therapeutic approaches in cancer. Furthermore, Protein-Protein Interaction (PPI) network analysis identified TOP2A and KIF4A as hub genes that may be important for aneuploidy establishment.

yearjournalcountryeditionlanguage
2019-08-27
10.1016/j.ygeno.2020.02.006http://hdl.handle.net/10447/406676