Wang Ruifeng, Wang Xiaobing, Zhuang Liwei
Gastroenterology and Hepatology Department, the Forth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
Gastroenterology and Hepatology Department, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
Ann Hepatol. 2016 Mar-Apr;15(2):190-9. doi: 10.5604/16652681.1193709.
Background. This study aims to identify key genes and pathways involved in non-alcoholic fatty liver disease (NAFLD).
The dataset GSE48452 was downloaded from Gene Expression Omnibus, including 14 control liver samples, 27 healthy obese samples, 14 steatosis samples and 18 nonalcoholic steatohepatitis (NASH) samples. Differentially expressed genes (DEGs) between controls and other samples were screened through LIMMA package. Then pathway enrichment analysis for DEGs was performed by using DAVID, and alterations of enriched pathways were determined. Furthermore, protein-protein interaction (PPI) networks were constructed based on the PPI information from HPRD database, and then, networks were visualized through Cytoscape. Additionally, interactions between microRNAs (miRNAs) and pathways were analyzed via Fisher's exact test.
A total of 505, 814 and 783 DEGs were identified for healthy obese, steatosis and NASH samples in comparison with controls, respectively. DEGs were enriched in ribosome (RPL36A, RPL14, etc.), ubiquitin mediated proteolysis (UBE2A, UBA7, etc.), focal adhesion (PRKCA, EGFR, CDC42, VEGFA, etc.), Fc?R-mediated phagocytosis (PRKCA, CDC42, etc.), and so on. The 27 enriched pathways gradually deviated from baseline (namely, controls) along with the changes of obese-steatosis-NASH. In PPI networks, PRKCA interacted with EGFR and CDC42. Besides, hsa-miR-330-3p and hsa-miR-126 modulated focal adhesion through targeting VEGFA and CDC42.
The identified DEGs (PRKCA, EGFR, CDC42, VEGFA), disturbed pathways (ribosome, ubiquitin mediated proteolysis, focal adhesion, Fc?R-mediated phagocytosis, etc.) and miRNAs (hsa-miR-330-3p, hsa-miR-126, etc.) might be closely related to NAFLD progression. These results might contribute to understanding NAFLD mechanism, conducting experimental researches, and designing clinical practices.
背景。本研究旨在确定非酒精性脂肪性肝病（NAFLD）中涉及的关键基因和通路。
从基因表达综合数据库下载数据集GSE48452，包括14个对照肝脏样本、27个健康肥胖样本、14个脂肪变性样本和18个非酒精性脂肪性肝炎（NASH）样本。通过LIMMA软件包筛选对照样本与其他样本之间的差异表达基因（DEG）。然后使用DAVID对DEG进行通路富集分析，并确定富集通路的变化。此外，基于HPRD数据库中的蛋白质-蛋白质相互作用（PPI）信息构建PPI网络，然后通过Cytoscape对网络进行可视化。另外，通过Fisher精确检验分析微小RNA（miRNA）与通路之间的相互作用。
与对照相比，分别在健康肥胖、脂肪变性和NASH样本中鉴定出505、814和783个DEG。DEG富集于核糖体（RPL36A、RPL14等）、泛素介导的蛋白水解（UBE2A、UBA7等）、粘着斑（PRKCA、EGFR、CDC42、VEGFA等）、FcγR介导的吞噬作用（PRKCA、CDC42等）等。随着肥胖-脂肪变性-NASH的变化，27条富集通路逐渐偏离基线（即对照）。在PPI网络中，PRKCA与EGFR和CDC42相互作用。此外，hsa-miR-330-3p和hsa-miR-126通过靶向VEGFA和CDC42调节粘着斑。
鉴定出的DEG（PRKCA、EGFR、CDC42、VEGFA）、受干扰的通路（核糖体、泛素介导的蛋白水解、粘着斑、FcγR介导的吞噬作用等）和miRNA（hsa-miR-330-3p、hsa-miR-126等）可能与NAFLD的进展密切相关。这些结果可能有助于理解NAFLD的机制、开展实验研究以及设计临床实践。
