生物信息学分析丁酸盐调控肝细胞癌细胞周期的作用机制OA

Objective To investigate the potential association between butyrate and cell cycle regulatory genes of hepatocellular carcinoma(HCC)based on bioinformatics,and explore the effect and mechanism of butyrate against HCC.Methods CCK-8 assay was used to detect the inhibitory effect of butyrate on the proliferation of HCC cells and verify its in vitro anti-tumor activity.Differentially expressed genes(DEGs)between HCC tissues and normal liver tissues were screened based on the UCSC Xena database.Key gene sets signifi-cantly positively correlated with HCC phenotypic traits were further identified by survival analysis and weighted gene co-expression network analysis(WGCNA).Genes interacting with butyrate were retrieved from CTD database,and intersected with the key gene sets posi-tively correlated with HCC phenotypes to screen potential overlapping genes.The expression differences of BIRC5,CDC20,KIF20A and CDK1 proteins between HCC tissues and adjacent non-cancerous tissues were analyzed using TCGA database and THPA website.The correlations of the above four proteins with the survival time of HCC patients were analyzed via the ONCOLNC database.The protein interaction relationships among BIRC5,CDC20,KIF20A and CDK1 were analyzed based on the STRING database.Results CCK-8 assay results showed that butyrate inhibited the growth of HCC cells in a dose-dependent manner(P<0.05).Bioinformatics analysis identified 1 604 up-regulated genes and 2 049 down-regulated genes in HCC tissues compared with adjacent non-cancerous tissues(P<0.05).WGCNA revealed that genes in the turquoise module were significantly positively correlated with HCC tissue phenotypes(P<0.05).Venn intersection analysis showed an overlap between turquoise module signature genes and butyrate-related genes annotated in the CTD database,and four core genes were finally screened out:BIRC5,CDC20,KIF20A and CDK1.The results from TCGA database and THPA website confirmed that BIRC5,CDC20,KIF20A and CDK1 were highly expressed in HCC tissues(P<0.05).HCC patients with high expression of these genes exhibited shorter survival time than those with low expression(P<0.05).STRING database analysis indicated that BIRC5,CDC20,KIF20A and CDK1 proteins interacted with each other.Conclusion Butyrate can impede HCC cell cycle progression and inhibit cancer cell proliferation by regulating the BIRC5,CDC20,KIF20A,CDK1 gene network,which provides potential molecular targets for the clinical application of butyrate in treatment of HCC.