Abstract
Purpose There is growing awareness of critical roles of circular RNA (circRNA) in tumor growth and development. This study aimed to discover new cancer-promoting circRNAs and to study their potential roles in the pathogenesis of hepatocellular carcinoma (HCC). Methods The expression profiles and clinical data of HCC-related circRNA, miRNA, and mRNA were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A model of the circRNA-miRNA-mRNA network was established based on analysis and interaction prediction. The main biological functions of the targeted mRNA were predicted by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the protein-protein interaction (PPI) network was constructed to reveal important hub genes. The online tool OncomiR and GEPIA were used to analyze the correlation between miRNA and mRNA and clinicopathological features, and the Kaplan-Meier curve was constructed to reveal the relationship between mRNA and patient prognosis. Results Differential analysis indicated that twenty highly expressed circRNA in GEO microarray datasets GSE78520, GSE94508, and GSE97332. Ten miRNAs were targeted by 20 circRNAs. These miRNAs are expressed at lower levels in the TCGA liver hepatocellular carcinoma (LIHC) expression profile, and most of the functions of these genes are closely related to pathological staging. These 10 miRNAs predicted a total of 7310 downstream mRNAs, of which 169 mRNAs were more abundant than normal tissues in the TCGA LIHC expression profile. GO analysis, KEGG analysis, and protein-protein interaction network analysis showed that E2F1, H2AFX, TOP2A, and RAD51 are central genes of the competitive endogenous RNA (ceRNA) network, and are mainly involved in biological mechanisms such as cell cycle, cancer-related pathways, and blood vessel morphogenesis. In addition, E2F1, H2AFX, TOP2A, and RAD51 are also closely related to the pathological stage and survival of patients. Conclusions The analysis allowed the construction of a competitive endogenous RNA network associated with cancer-promoting circRNAs. Genes involved in this network may provide potential therapeutic targets for the diagnosis and treatment of HCC.
The expression profile of Jagged1 and Delta-like 4 in hepatocellular carcinoma
