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

by Selleckchem | Mar 28 2023

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.

Comments：

This study investigated the role of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC) and their potential as diagnostic and therapeutic targets. The researchers constructed a ceRNA and survival network using Cytoscape and performed various analyses using R, Perl software, and multiple online databases and platforms, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

Their KEGG analysis revealed the T cell receptor signaling pathway as the main enrichment pathway, and they identified 29 genes related to survival and prognosis. Further analysis showed that ZNF544, WDR76, ACTG1, RASSF3, E2F3, ASRGL1, and POGK were associated with multilevel immune cell infiltration, and the immune checkpoint analysis screened out the ACTG1, E2F3, RASSF3, and WDR76 genes. The study also found that the WDR76, E2F3, ASRGL1, and POGK genes mainly activated the cell cycle and DNA damage response (DDR) pathway.

The researchers found that the sensitivity toward trametinib, refametinib (RDEA119), and selumetinib correlated with the expression of WDR76. Additionally, their ROC analysis showed that 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.

Overall, this study provides valuable insights into the role of circRNAs in HCC and identifies potential diagnostic and therapeutic targets for the disease.