title: Gene expression profiling reveals key genes and pathways related to the development of non-alcoholic fatty liver disease.
abstract: Background. This study aims to identify key genes and pathways involved in non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Gastroenterology and Hepatology Department, the Forth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors: Ruifeng
authors: R
authors: Wang
authors: Gastroenterology and Hepatology Department, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors: Xiaobing
authors: X
authors: Wang
authors: Gastroenterology and Hepatology Department, the Forth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors: Liwei
authors: L
authors: Zhuang
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D030541:Databases, Genetic; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism; D000067329:Obesity, Metabolically Benign / Q000235:genetics* / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics; D060066:Protein Interaction Maps; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012269:Ribosomal Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D044763:Ubiquitin-Conjugating Enzymes; C512478:EGFR protein, human; D066246:ErbB Receptors; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D020764:cdc42 GTP-Binding Protein