Identification of a novel circRNA–miRNA–mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis

Abstract

In recent years, circular RNAs (circRNAs) have been found to play an essential regulatory role in hepatocellular carcinoma (HCC) through various mechanisms, particularly the endogenous competitive RNA (ceRNA) mechanism. Therefore, it is significant to explore the circRNAs in hepatoma. In this study, we constructed the ceRNA and survival network using Cytoscape. We also used R, Perl software, and multiple online databases and platforms, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), to perform overall survival, immune cell infiltration, immune checkpoints, pathway activity, and anticancer drug sensitivity analysis of the genes. Finally, the receiver operator characteristic curve (ROC) analysis was performed to identify the diagnosis value of the genes. KEGG analysis revealed the T cell receptor signaling pathway as the main enrichment pathway. A total of 29 genes related to survival and prognosis were screened out. The findings suggest that ZNF544, WDR76, ACTG1, RASSF3, E2F3, ASRGL1, and POGK are associated with multilevel immune cell infiltration. Additionally, immune checkpoint analysis screened out the ACTG1, E2F3, RASSF3, and WDR76. It was also revealed that the WDR76, E2F3, ASRGL1, and POGK mainly activated the cell cycle and DNA damage response (DDR) pathway. The results suggest that the sensitivity toward trametinib, refametinib (RDEA119), and selumetinib correlates to the expression of WDR76. ROC analysis showed that the area under the curve (AUC) of all genes in the regulatory axis was greater than 0.7. The identified hsa_circ_0000417/hsa_circ_0002688/hsa_circ_0001387--hsa-miR-199a-5p--WDR76 regulatory axis may provide new insights into the progression, clinical diagnosis, and treatment of HCC.

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

“…Bioinformatic-based techniques have speeded up the identification of HCC-related circ RNAs (205)(206)(207), such as circMRD27 which mediates resistance to levantinib (208). Previously we have reviewed the role of circular RNAs in breast cancer (209,210), esophageal squamous cell carcinoma (211) and colorectal cancer (212).…”

The novel circRNA hsa_circ_0000038 inhibits the progression of hepatocellular carcinoma by sponging miR-92a-2-5p to regulate the p53/p21 proteins

“…Mounting evidence indicates that circRNAs are involved in the development of HCC via sponging miRNAs to alter the activity of signaling pathways and host genes (10,11). For example, circMAPK9 sponges miR642 and affects the progression of HCC.…”