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

Abstract

Long noncoding RNA s (lncRNA s) act as competing endogenous RNA s (ceRNA s) 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 lncRNA s (DE lncRs), miRNA s (DE miRs), and mRNA s (DE Gs) between tumoral and control samples were identified using the edgeR package. The correlations between the DemiR/DE lncR expression levels and clinical features were evaluated using nonparametric regression analysis. The Kaplan-Meier method was used to identify DE lncRs associated with overall survival time. Then, the DE lncR-DE miR interaction pairs were predicted using miRcode and the starBase v2.0 database, and DE miR-DE G 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 DE Gs, 37 DelncRs, and 62 DE miRs were identified. Moreover, several DE lncRs were significantly associated with patient clinical variables; for example, TCL 6 was significantly associated with tumor grade and AJCC pathological stage. Next, 38 pairs of DE lncR-DE miR interactions (13 DElncRs and 8 DEmiRs) were identified. Among the 8 DE miRs that target DE lncRs, 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- p2 >0.15). The novel lncRNA s, DGCR 5, MYCNO S, and PAR T1 may participate in the progression of ccRCC through cytochrome P450-mediated drug metabolism.