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

机译:通过耗尽PRB,DNMT1和MAD2诱导的一种细胞诱导的常见基因表达签名

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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.
机译:染色体分离缺陷导致非整倍性,这是固体瘤的主要特征。二倍体细胞面临染色体的误解以及非整倍性在肿瘤细胞中如何仍然是如何仍然完全定义的。因此,癌症遗传学的一个重要目标是鉴定基因网络,该基因网络是非整倍性的,并且参与其耐受性。为此目的,我们通过耗尽PRB,DNMT1和MAD2,通过微阵列分析分析它们的基因表达谱,诱导IMR90人体原代细胞中的非倍性。生物信息分析显示了含有动脉倍体的IMR90细胞的常见基因表达谱。基因设定富集分析(GSEA)还揭示了由组织型IMR90细胞共享的基因组/途径,其可用于癌症中的新疗法方法。此外,蛋白质 - 蛋白质相互作用(PPI)网络分析鉴定为TOP2A和KIF4A,为对非整倍性建立可能重要的枢纽基因。

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