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Identification of β-catenin target genes in colorectal cancer by interrogating gene fitness screening data

机译:询问基因适应性筛选数据鉴定大肠癌中β-catenin靶基因

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摘要

β-catenin regulates its target genes which are associated with proliferation, differentiation, migration and angiogenesis, and the dysregulation of Wnt/β-catenin signaling facilitates hallmarks of colorectal cancer (CRC). Identification of β-catenin targets and their potential roles in tumorigenesis has gained increased interest. However, the number of identified targets remains limited. The present study implemented a novel strategy, interrogating gene fitness profiles derived from large-scale RNA interference and CRISPR-CRISPR associated protein 9 screening data to identify β-catenin target genes in CRC cell lines. Using these data sets, pair wise gene fitness similarities were determined which highlighted a total of 13 genes whose functions were highly correlated with β-catenin. It was further demonstrated that the expression of these genes were altered in CRC, illustrating their potential roles in the progression of CRC. The present study further demonstrated that these targets could be used to predict disease-free survival in CRC. In conclusion, the findings provided novel approaches for the identification of β-catenin targets, which may become prognostic biomarkers or drug targets for the management of CRC.
机译:β-catenin调节与增殖,分化,迁移和血管生成相关的靶基因,而Wnt /β-catenin信号的失调促进结直肠癌(CRC)的特征。鉴定β-连环蛋白靶标及其在肿瘤发生中的潜在作用已引起越来越多的关注。但是,确定的目标数量仍然有限。本研究实施了一种新的策略,询问源自大规模RNA干扰和CRISPR-CRISPR相关蛋白9筛选数据的基因适应性谱,以鉴定CRC细胞系中的β-连环蛋白靶基因。使用这些数据集,确定了成对的基因适应性相似性,突出显示了总共13个基因的功能与β-catenin高度相关。进一步证明这些基因在CRC中的表达发生了改变,说明了它们在CRC进展中的潜在作用。本研究进一步证明,这些靶标可用于预测CRC的无病生存期。总之,这些发现提供了鉴定β-catenin靶标的新方法,β-catenin靶标可能成为CRC治疗的预后生物标志物或药物靶标。

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