Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

AIM To discover methylated-differentially expressed genes(MDEGs) in hepatocellular carcinoma(HCC) and to explore relevant hub genes and potential pathways. METHODS The data of expression profiling GSE25097 and methylation profiling GSE57956 were gained from GEO Datasets. We analyzed the differentially methylated genes and differentially expressed genes online using GEO2 R. Functional and enrichment analyses of MDEGs were conducted using the DAVID database. A protein-protein interaction(PPI) network was performed by STRING and then visualized in Cytoscape. Hub genes were ranked by cytoH ubba, and a module analysis of the PPI network was conducted by MCODE in Cytoscape software. RESULTS In total, we categorized 266 genes as hypermethylated, lowly expressed genes(Hyper-LGs) referring to endogenous and hormone stimulus, cell surface receptor linked signal transduction and behavior. In addition, 161 genes were labelled as hypomethylated, highly expressed genes(Hypo-HGs) referring to DNA replication and metabolic process, cell cycle and division. Pathway analysis illustrated that Hyper-LGs were enriched in cancer, Wnt, and chemokine signalling pathways, while Hypo-HGs were related to cell cycle and steroid hormone biosynthesis pathways. Based on PPI networks, PTGS2, PIK3 CD, CXCL1, ESR1, and MMP2 were identified as hub genes for Hyper-LGs, and CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10 were hub genes for Hypo-HGs by combining six ranked methods of cytoH ubba. CONCLUSION In the study, we disclose numerous novel genetic and epigenetic regulations and offer a vital molecular groundwork to understand the pathogenesis of HCC. Hub genes, including PTGS2, PIK3 CD, CXCL1, ESR1, MMP2, CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10, can be used as biomarkers based on aberrant methylation for the accurate diagnosis and treatment of HCC.

Morin enhances hepatic Nrf2 expression in a liver fibrosis rat model

AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride(CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimenswere obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin(α-SMA), collagen Ⅰ, collagen Ⅲ, Nrf2, heme oxygenase(HO-1), and quinone oxidoreductase 1(NQO1) using frozen liver specimens.RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower m RNA and protein expression of α-SMA, collagen Ⅰ, and collagen Ⅲ, but significantly higher m RNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only(P < 0.05).CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors(HO-1 and NQO1) and reducing the expression of α-SMA, collagen Ⅰ, and collagen Ⅲ in CCl4-induced liver fibrosis rats.