Cancer is a disease caused by (epi)genomic and gene expression abnormalities and characterized by metabolic phenotypes that are substantially different from the normal phenotypes of the tissues of origin. Metabolic reprogramming is one of the key features of tumors, including those established in the human nervous system. In this work, we emphasize a well-known cancerous genomic alteration: the amplification ofMYCNand its downstream effects in neuroblastoma phenotype evolution. Herein, we extend our previous computational biology investigations by conducting an integrative workflow applied to published genomics datasets and comprehensively assess the impact ofMYCNamplification in the upregulation of metabolism-related transcription factor (TF)-encoding genes in neuroblastoma cells. The results obtained first emphasized overexpressed TFs, and subsequently those committed in metabolic cellular processes, as validated by gene ontology analyses (GOs) and literature curation. Several genes encoding for those TFs were investigated at the mechanistic and regulatory levels by conducting further omics-based computational biology assessments applied on published ChIP-seq datasets retrieved fromMYCN-amplified- andMYCN-enforced-overexpression within in vivo systems of study. Hence, we approached the mechanistic interrelationship between amplifiedMYCNand overexpression of metabolism-related TFs in neuroblastoma and showed that many are direct targets of MYCN in an amplification-inducible fashion. These results illuminate howMYCNexecutes its regulatory underpinnings on metabolic processes in neuroblastoma.
癌症是一种由（表观）基因组和基因表达异常引起的疾病，其代谢表型与起源组织的正常表型存在显著差异。代谢重编程是肿瘤的关键特征之一，包括发生在人类神经系统中的肿瘤。本研究聚焦于一个众所周知的癌症基因组改变：MYCN基因的扩增及其在神经母细胞瘤表型演变中的下游效应。在此，我们通过将整合分析流程应用于已发表的基因组学数据集，扩展了先前的计算生物学研究，全面评估了MYCN扩增对神经母细胞瘤细胞中代谢相关转录因子编码基因上调的影响。研究结果首先强调了过表达的转录因子，随后通过基因本体分析和文献梳理，验证了这些因子参与细胞代谢过程。针对编码这些转录因子的若干基因，我们通过进一步应用基于组学的计算生物学评估方法，对从MYCN扩增型及在体内研究系统中强制过表达MYCN所获取的已发表ChIP-seq数据集进行了机制和调控层面的研究。因此，我们探讨了神经母细胞瘤中MYCN扩增与代谢相关转录因子过表达之间的机制性相互关系，并证明其中许多转录因子是MYCN以扩增诱导方式的直接靶标。这些结果阐明了MYCN如何在神经母细胞瘤中执行其对代谢过程的调控基础。
肿瘤(癌症)患者之家