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Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system, and its early asymptomatic characteristic increases the difficulty of diagnosis and treatment. This study is aimed at obtaining some novel biomarkers with diagnostic and prognostic meaning and may find out potential therapeutic targets for HCC. We screen differentially expressed genes (DEGs) from the HCC gene expression profile GSE14520 using GEO2R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by using the clusterProfiler software while a protein-protein interaction (PPI) network was performed based on the STRING database. Then, prognosis analysis of hub genes was conducted using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to further verify the expression of hub genes and explore the correlation between gene expression and clinicopathological parameters. A total of 1053 DEGs were captured, containing 497 upregulated genes and 556 downregulated genes. GO and KEGG analysis indicated that the downregulated DEGs were mainly enriched in the fatty acid catabolic process while upregulated DEGs were primarily enriched in the cell cycle. Simultaneously, ten hub genes (CYP3A4, UGT1A6, AOX1, UGT1A4, UGT2B15, CDK1, CCNB1, MAD2L1, CCNB2, and CDC20) were identified by the PPI network. Five prognosis-related hub genes (CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20) were uncovered by the survival analysis based on TCGA database. The ten hub genes were further validated by qRT-PCR using samples obtained from our hospital. The prognosis-related hub genes such as CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20 could be considered potential diagnosis biomarkers and prognosis targets for HCC. We also use Oncomine for further verification, and we found CCNB1, CCNB2, CDK1, and CYP3A4 which were highly expressed in HCC. Meanwhile, CCNB1, CCNB2, and CDK1 are highly expressed in almost all cancer types, which may play an important role in cancer. Still, further functional study should be conducted to explore the underlying mechanism and biological effect in the near future. [ABSTRACT FROM AUTHOR]

Background and Aim. Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis. Methods. Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results. MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion. Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis. [ABSTRACT FROM AUTHOR]