Construction of a circRNA-miRNA-mRNA Network Related to Macrophage Infiltration in Hepatocellular Carcinoma

Abstract

Immune cells in the tumor microenvironment play a crucial role in regulating tumor progression. The circular RNA (circRNA) regulatory network involved in immune cell infiltration in hepatocellular carcinoma (HCC) remains largely unknown. In this study, the “estimate the proportion of immune and cancer cells” (EPIC) application is used to evaluate the fractions of immune cells, cancer-associated fibroblasts, and endothelial cells in HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Patients with a high macrophage fraction have better overall survival, and macrophage fraction is an independent prognostic factor for HCC. Next, the common differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) between paired tumor and non-tumor tissues are screened out from the TCGA and/or GEO databases. Through spearman correlation analysis, the macrophage-related DEmRNAs are identified to construct a circRNA-miRNA-mRNA regulatory network, which includes 6 DEcircRNAs, 7 DEmiRNAs, and 45 DEmRNAs. Functional enrichment analysis reveals that these DEmRNAs are mainly involved in immune-related processes. Furthermore, six hub DEmRNAs are identified to establish a hub circRNA regulatory network. Among the DEmRNAs in the network, PRC1 is identified as the most influential node. PRC1 high expression is correlated with poor prognosis and low macrophage infiltration in HCC. Taken together, we identify a certain circRNA regulatory network related to macrophage infiltration and provide novel insight into the mechanism of study and therapeutic targets for HCC.