Identification of the Glucose Metabolism Biomarkers of NASH: Weighted Gene Co-Expression Network Analysis

Abstract Background The genetic mechanism of glucose metabolism has not been elucidated in nonalcoholic steatohepatitis (NASH), and many genes are took part in glucose metabolism of NASH. In this study, we used the weighted gene co-expression network analysis (WGCNA) to find the key genes associated with glucose metabolism; Methods Data sets GSE96971 and GSE89632 from Gene Expression Omnibus (GEO) were analyzed by WGCNA. We screened the Hub gene from the GSE96971 dataset, and the selected Hub genes were verified by GSE89632 dataset. We then analyzed the dataset using the Gene Ontology (GO) term enrichment and the Kyoto Encyclopedia of Genome (KEGG) path analysis. Expression levels of the hub genes are assessed by qPCR analysis. The function of hub genes was verified by Nile Red staining and relative glucose consumption detection; Results The hub genes are mannosidase beta like (MANBAL), myc proto-oncogene protein (MYC), caspase 4 (CASP4), CDK5 regulatory subunit associated protein 3 (CDK5RAP3) and ZFP36 ring finger protein (ZFP36) in the datasets GSE96971 and the GSE89632. Further, these genes are mainly involved in the integral component of membrane and plasma membrane, the PI3K-AKT signaling pathway and the olfactory transduction according to the GO and KEGG results. These hub genes were significantly up-regulated in the palmitic acid (PA) cell model and methionine-choline-deficient medium (MCD) cell model. After knocking out the hub genes in PA model and the MCD model of NASH, relative glucose consumption was increased and lipid deposition was reduced compared with the control group; Conclusions MANBAL, MYC, CASP4, CDK5RAP3 and ZFP36 are elevated and involved in the pathogenesis of NASH. Further research on these genes are warranted.