Exploring Shared Genetic Features and Molecular Mechanisms between Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma through Bioinformatics.

BACKGROUND: Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world, characterized by high incidence, high malignancy, and low survival rate. Currently, 1/4 of adults in the world suffer from Non-Alcoholic Fatty Liver Disease (NAFLD), with an incidence rate of 27% in Asia. METHODS: We used TCGA and GEO public database data sets to conduct weighted gene coexpression network analysis to identify relevant gene modules, defined the intersection of tumorigenesis-related modules and NASH development-related modules as shared genes, and then used single-factor Cox, LASSO, and multivariate Cox regression analysis screened out core shared genes and verified their prognostic value. We further investigated the relationship between core shared genes and immune infiltration, tumor mutational load, and drug sensitivity. Finally, RT-qPCR was used to verify its mRNA expression in different cell lines. RESULTS: We identified Karyopherin α 2 (KPNA2) as the core shared gene between NASH and HCC. Patients were divided into low-risk groups and high-risk groups based on the expression of KPNA2. The prognosis of the low-risk group was significantly better than that of the highrisk group. Furthermore, we found significant differences in tumor immune cell infiltration, somatic mutations, microsatellite instability, and drug sensitivity between different expression groups. CONCLUSION: There are very few studies on the molecular mechanism of the relationship between NAFLD and HCC. Our study demonstrates that KPNA2 is a potential therapeutic target and immune-related biomarker for patients with NAFLD and HCC.

Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration.

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.