A ferroptosis-related ceRNA network in hepatocellular carcinoma for potential clinical applications

Objective: To explore the competing endogenous RNA (ceRNA) network related to ferroptosis in hepatocellular carcinoma (HCC) and its promise for clinical application.

Methods: We obtained RNA sequencing data for HCC and relevant clinical information from The Cancer Genome Atlas (TCGA) database. To assess the involvement of the autophagy, pyroptosis, and ferroptosis pathways in HCC, we used single-sample Gene Set Enrichment Analysis (ssGSEA) to compute scores for each sample based on pre-defined gene sets. We conducted Weighted Gene Co-Expression Network Analysis (WGCNA) to effectively modularize lncRNA, miRNA, and mRNA. Through extensive correlation analyses, we pinpointed the most crucial ferroptosis-associated modules. Moreover, we utilized online prediction tools to construct a corresponding ceRNA network. To establish the reliability of our results, we randomly chose a ceRNA axis consisting of DNAJC27-AS1/miR-23b-3p/PPIF for experimental validation. We performed luciferase reporter assays to validate the binding sites of DNAJC27-AS1, miR-23b-3p, and PPIF.

Results: We found a significant correlation between the level of ferroptosis and the overall survival of patients with HCC. Thus, we constructed a comprehensive ferroptosis-related ceRNA network. Our experimental findings revealed that DNAJC27-AS1 and PPIF act as direct sponges of miR-23b-3p, and thus are capable of downregulating ferroptosis in HCC cells.

Conclusion: The ferroptosis-associated ceRNA network presented in this study represents a valuable resource for advancing our understanding of the role of ferroptosis in HCC.