Abstract
Background: Circular RNAs (circRNAs) are known to be closely involved in tumorigenesis and cancer progression. Nevertheless, their function and underlying mechanisms in renal cell carcinoma (RCC) remain largely unknown. The aim of the present study was to explore their expression, functions, and molecular mechanisms in RCC.Methods: We downloaded the circRNA expression profiles from Gene Expression Omnibus (GEO) database, and RNA expression profiles from The Cancer Genome Atlas (TCGA) database. A ceRNA network was constructed based on circRNA–miRNA pairs and miRNA–mRNA pairs. Interactions between proteins were analyzed using the STRING database, and hub genes were identified using the cytoHubba app. We also constructed a circRNA–miRNA–hub gene regulatory module. Functional and pathway enrichment analyses were conducted using “DAVID 6.8” and R package “clusterProfiler”.Results: About 6 DEcircRNAs, 17 DEmiRNAs, and 134 DEmRNAs were selected for the construction of ceRNA network of RCC. Protein–protein interaction network and module analysis identified 8 hub genes. A circRNA–miRNA–hub gene sub-network was constructed based on 3 DEcircRNAs, 4 DEmiRNAs, and 8 DEmRNAs. GO and KEGG pathway analysis indicated the possible association of DEmRNAs with RCC onset and progression.Conclusions: These findings together provide a deeper understanding of the pathogenesis of RCC and suggest potential therapeutic targets.
Highlights
Renal cell carcinoma (RCC) is one of the most common urological malignancies, accounting for 2–3% of all adult tumors, and is only secondary to bladder cancer
The target miRNAs were compared to differentially expressed miRNA (DEmiRNA) based on The Cancer Genome Atlas (TCGA); only overlapping genes were selected as candidate genes
The DEmiRNAs and DEmRNAs, obtained from the TCGA database, were analyzed across renal cell carcinoma (RCC) tissues and adjacent normal tissues; we identified 187 DEmiRNAs (135 up-regulated and 52 down-regulated), and 5029 DEmRNAs (3681 up-regulated and 1348 down-regulated) (Figure 3A,B)
Summary
Renal cell carcinoma (RCC) is one of the most common urological malignancies, accounting for 2–3% of all adult tumors, and is only secondary to bladder cancer. Despite the recent efforts in multimodal approaches, the prognosis of patients with RCC remains poor This situation is mainly due to delayed diagnosis, high-frequent metastasis, and recurrence after surgery [3,4]. CircRNA is abundant in eukaryotic cells, highly conserved, and structurally stable, with a certain degree of organization, timing, and disease-specificity [7,8]. Circular RNAs (circRNAs) are known to be closely involved in tumorigenesis and cancer progression. Their function and underlying mechanisms in renal cell carcinoma (RCC) remain largely unknown. A circRNA–miRNA–hub gene sub-network was constructed based on 3 DEcircRNAs, 4 DEmiRNAs, and 8 DEmRNAs. GO and KEGG pathway analysis indicated the possible association of DEmRNAs with RCC onset and progression. Conclusions: These findings together provide a deeper understanding of the pathogenesis of RCC and suggest potential therapeutic targets
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