Biotechnology Graduate Program, American University, New Cairo, 11835, Egypt.
Department of Chemistry, The American University in Cairo, School of Sciences & Engineering, New Cairo, 11835, Egypt.
Sci Rep. 2018 Sep 24;8(1):14234. doi: 10.1038/s41598-018-32464-5.
Understanding the transcriptional regulatory elements that influence the progression of liver disease in the presence of hepatitis C virus (HCV) infection is critical for the development of diagnostic and therapeutic approaches. Systems biology provides a roadmap by which these elements may be integrated. In this study, a previously published dataset of 124 microarray samples was analyzed in order to determine differentially expressed genes across four tissue types/conditions (normal, cirrhosis, cirrhosis HCC, and HCC). Differentially expressed genes were assessed for their functional clustering and those genes were annotated with their potential transcription factors and miRNAs. Transcriptional regulatory networks were constructed for each pairwise comparison between the 4 tissue types/conditions. Based on our analysis, it is predicted that the disruption in the regulation of transcription factors such as AP-1, PPARγ, and NF-κB could contribute to the liver progression from cirrhosis to steatosis and eventually to HCC. Whereas the condition of the liver digresses, the downregulation of miRNAs' (such as miR-27, Let-7, and miR-106a) expression makes the transition of the liver through each pathological stage more apparent. This preliminary data can be used to guide future experimental work. An understanding of the transcriptional regulatory attributes acts as a road map to help design interference strategies in order to target the key regulators of progression of HCV induced HCC.
了解 HCV 感染时影响肝病进展的转录调控元件对于开发诊断和治疗方法至关重要。系统生物学为整合这些元件提供了路线图。在这项研究中，分析了之前发表的 124 个微阵列样本数据集，以确定四个组织类型/条件（正常、肝硬化、肝硬化 HCC 和 HCC）之间差异表达的基因。对差异表达的基因进行了功能聚类评估，并对其潜在的转录因子和 miRNA 进行了注释。为每个组织类型/条件之间的两两比较构建了转录调控网络。基于我们的分析，据预测，AP-1、PPARγ 和 NF-κB 等转录因子的调节紊乱可能导致肝脏从肝硬化进展为脂肪变性，最终发展为 HCC。随着肝脏状况恶化，miRNA（如 miR-27、Let-7 和 miR-106a）表达的下调使得肝脏通过每个病理阶段的转变更加明显。这些初步数据可用于指导未来的实验工作。了解转录调控属性可以作为一个路线图，帮助设计干扰策略，以针对 HCV 诱导 HCC 进展的关键调节剂。
