Identification of CircRNAs that promote cancer and their potential contribution to hepatocellular carcinoma (HCC) pathogenesis.

Abstract

The critical involvement of circRNAs in tumour progression and development is becoming increasingly evident. This study aimed to identify novel cancer-promoting circRNAs and explore their potential contribution to the pathogenesis of hepatocellular carcinoma (HCC). Expression profiles of circRNAs, miRNAs, and mRNAs associated with HCC were predicted through interaction analysis using data from the GEO and TCGA databases. A circRNA-miRNA-mRNA network was constructed, and the biological functions of the target mRNAs were predicted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was generated to identify important hub genes. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to determine the key modules related to cancer-promoting circRNAs. OncomiR and GEPIA were used to investigate the correlation between miRNAs, mRNAs, and clinicopathological features, while TIMER was utilized to explore the relationship between gene expression and immune cell infiltration. A network of 18 cancer-promoting circRNAs in HCC was identified, which enhanced the expression of 141 downstream mRNAs through competitive binding with 10 miRNAs. GO, KEGG, and PPI network analyses revealed that E2F1, H2AFX, TOP2A, and RAD51 are key hub genes within the competitive endogenous RNA (ceRNA) network, primarily involved in cell cycle regulation, cancer-related pathways, and angiogenesis. WGCNA identified the "HCC DUcircRNA Module". Moreover, these core genes and key modules were closely associated with pathological stage, patient survival, and B-cell immune infiltration. We constructed a ceRNA network related to cancer-promoting circRNAs. The genes and key modules involved in this network may serve as potential therapeutic targets.