Identification of key genes in non‑alcoholic fatty liver disease progression based on bioinformatics analysis

Abstract

Due to economic development and lifestyle changes, the incidence of non-alcoholic fatty liver disease (NAFLD) has gradually increased in recent years. However, the pathogenesis of NAFLD is not yet fully understood. To identify candidate genes that contribute to the development and progression of NAFLD, two microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified and functional enrichment analyses were performed. A protein-protein interaction network was constructed and modules were extracted using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. The enriched functions and pathways of the DEGs included ‘cellular macromolecule biosynthetic process’, ‘cellular response to chemical stimulus’, ‘extracellular matrix organization’, ‘metabolic pathways’, ‘insulin resistance’ and ‘forkhead box protein O1 signaling pathway’. The DEGs, including type-1 angiotensin II receptor, formin-binding protein 1-like, RNA-binding protein with serine-rich domain 1, Ras-related C3 botulinum toxin substrate 1 and polyubiquitin-C, were identified using multiple bioinformatics methods and validated in vitro with reverse transcription-quantitative polymerase chain reaction analysis. In conclusion, five hub genes were identified in the present study, and they may aid in understanding of the molecular mechanisms underlying the development and progression of NAFLD.

Insights into Molecular Mechanisms Underlying NAFLD by Protein-Protein Interaction Network Analysis of the Differentially Expressed Genes in NASH Patients.

“…We found a satisfactory agreement between our results and previous ndings on the role of genes in the disease's modulation. Also consistent with our results, biological processes such as focal adhesion, in ammatory response, brosis, and cellular response to chemical stimuli are highlighted in the literature (19)(20)(21).…”

“…This result was consistent with previous research, thus offering valuable evidence to study the complicated connection underlying the NASH disease. Accordingly, greater emphasis is placed on the AMPK signaling pathway, the insulin resistance pathway, and the Foxo signaling pathway in several research lines on NAFLD progression (21,40). Also included are several pathways involved in the cellular physiological processes linked to tumor cell proliferation, such as apoptosis, necroptosis, adherence junction, and cell cycle.…”

“…Using a bioinformatics analysis also, many hub genes that are essential to steatohepatitis development have been identi ed. For example, RPL36A, RPL14, UBE2A, UBE2B, PRKCA, EGFR, CDC42, VEGFA, PRKCA, CDC42, FCGR2A, and LARP1B were identi ed in GSE89632, GSE 33814, and GSE48452 datasets (1,2). Hub genes such as UBQLN4, APP, SHBG, CTNNB1, COL1A1, COL1A2, CD24, COL1A2, COL3A1, CXCL6, DCN, EHF, FAP, LUM, PCOLCE2, and SOX9 were all identi ed in a NAFLD-related brosis dataset (3,4).…”

Construction and Analysis of Protein-Protein Interaction Network of Non-Alcoholic Fatty Liver Disease

“…Interestingly, several studies applying bioinformatics analyses are in consistensy with our findings, revealing the possible implication of UBQLN4 [80], UBC [81] and PCNA [82] in NAFLD development as potential biomarkers. Likewise, a bioinformatics analysis in a PPI network of steatosis highlights CRK and MDM2 among of the top 10 important genes [83].…”

Palmitate and Fructose Interact to Induce Human Hepatocytes to Produce Pro-Fibrotic Transcriptional Responses in Hepatic Stellate Cells Exposed to Conditioned Media

“…In humans, fructose consumption for ten weeks led to increased hepatic de novo lipogenesis and 23-hour postprandial hypertriglyceridemia [ 14 ], suggesting that fructose may contribute to the development of NAFLD via the circulating lipid pool [ 8 ]. These data are consistent with recent evidence indicating that transcriptomic changes accompanying the early development of NAFLD occur predominantly in hepatocytes [ 24 ]. To date, however, the impact of palmitate- and fructose-treated human hepatocytes on transcriptomic changes in HSCs has not yet been characterized.…”