Comprehensive analysis of competing endogenous RNA networks involved in the regulation of glycolysis in clear cell renal cell carcinoma

Abstract

This study aims to elucidate the role of competing endogenous RNAs (ceRNAs), which are pivotal in the post-transcriptional regulation of cancer cells, in the glycolysis of clear cell renal cell carcinoma (ccRCC). RNA-seq data from ccRCC samples and public datasets were subjected to differential expression analysis to identify the upregulated circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and mRNAs for constructing a ceRNA network. This network focused on the upregulated mRNAs linked to glycolysis and gluconeogenesis, which were verified at the proteome level using the CPTAC database. The ENCORI database was used to predict the lncRNA/circRNA-miRNA and miRNA-mRNA interactions, which formed a network visualized using Cytoscape. This study further examined the association of selected lncRNAs/circRNAs with biological processes and patient survival and explored lncRNA and mRNA expressions at the single-cell level. Three circRNAs and eight lncRNAs were identified to be regulators of four glycolysis pathway genes (HK2, LDHA, PFKP, and ALDOC) via 54 miRNAs. Notably, their expressions were aberrant at the transcriptome and proteome levels. These RNA elements were correlated with malignant and immune pathways, and several lncRNAs showed prognostic significance for ccRCC. Furthermore, single-cell RNA sequencing indicated the abnormal enrichment of these lncRNAs and mRNAs in malignant cells. This study identified a ceRNA network that plays a critical role in the glycolysis of ccRCC. These findings highlight the importance of ceRNAs in cancer malignancy and their potential impact on patient prognosis.