Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Italy.
Fondazione Ri.MED, Palermo, Italy.
Genomics. 2020 May;112(3):2541-2549. doi: 10.1016/j.ygeno.2020.02.006. Epub 2020 Feb 10.
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.
染色体分离缺陷导致非整倍体，这是非整倍体肿瘤的主要特征。然而，二倍体细胞如何面对染色体错误分离，以及非整倍体在肿瘤细胞中如何被容忍，这些尚未完全确定。因此，癌症遗传学的一个重要目标是鉴定基础非整倍体并参与其耐受的基因网络。为此，我们通过耗尽 pRB、DNMT1 和 MAD2 诱导 IMR90 人原代细胞的非整倍体，并通过微阵列分析分析它们的基因表达谱。生物信息学分析揭示了 IMR90 细胞成为非整倍体的常见基因表达谱。基因集富集分析（GSEA）还揭示了非整倍体 IMR90 细胞共享的基因集/途径，这些基因集/途径可能被用于癌症的新治疗方法。此外，蛋白质-蛋白质相互作用（PPI）网络分析鉴定 TOP2A 和 KIF4A 作为可能对非整倍体建立很重要的枢纽基因。
