Identification of a lncRNA-associated competing endogenous RNA-regulated network in clear cell renal cell carcinoma

Long noncoding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) in the regulation of gene expression in various physiological and pathological processes. The present study aimed to explore the lncRNA-miRNA-mRNA interactions in clear cell renal cell carcinoma (ccRCC) using comprehensive bioinformatics analysis. RNA-seq data were downloaded from the TCGA Data Portal, and the differentially expressed lncRNAs (DElncRs), miRNAs (DEmiRs), and mRNAs (DEGs) between tumoral and control samples were identified using the edgeR package. The correlations between the DemiR/DElncR expression levels and clinical features were evaluated using nonparametric regression analysis. The Kaplan-Meier method was used to identify DElncRs associated with overall survival time. Then, the DElncR-DEmiR interaction pairs were predicted using miRcode and the starBase v2.0 database, and DEmiR-DEG pairs were predicted using the miRTarBase database. Then, a ceRNA-regulated network of ccRCC was constructed based on these interactions. Genes in the network were also assigned to functional categories in the KEGG pathway database. A total of 1,573 DEGs, 37 DelncRs, and 62 DEmiRs were identified. Moreover, several DElncRs were significantly associated with patient clinical variables; for example, TCL6 was significantly associated with tumor grade and AJCC pathological stage. Next, 38 pairs of DElncR-DEmiR interactions (13 DElncRs and 8 DEmiRs) were identified. Among the 8 DEmiRs that target DElncRs, six were found to target DEGs. Based on the identified DElncR-DEmiR interactions and DEmiR-DEG interactions, a ceRNA-regulated network comprising 203 nodes and 221 edges was constructed (with MIC >0.15 and MIC-p(2) >0.15). The novel lncRNAs, DGCR5, MYCNOS, and PART1 may participate in the progression of ccRCC through cytochrome P450-mediated drug metabolism.