Identification of hsa_circ_0002024 as a prognostic competing endogenous RNA (ceRNA) through the hsa_miR_129-5p/Anti-Silencing Function 1B Histone Chaperone (ASF1B) axis in renal cell carcinoma

Abstract

We aimed to identify novel circular RNAs (circRNAs) as prognostic competing endogenous RNAs (ceRNAs) to serve as genetic biomarkers and therapeutic targets for renal cell carcinoma (RCC). High-throughput sequencing data of circRNAs from Gene Expression Omnibus (GEO) and of microRNAs (miRNAs) and messenger RNAs (mRNAs) from The Cancer Genome Atlas (TCGA) were retrieved to identify differentially expressed RNAs (DERNAs). DEmRNAs were subjected to weighted gene coexpression network analysis (WGCNA) to identify prognostic DEmRNA (proDEmRNA) modules. Overlapping DEcircRNA-DEmiRNA and DEmiRNA-proDEmRNA interactions among the TargetScan, miRanda and RNAhybrid databases were constructed and identified. The circRNA-miRNA-mRNA ceRNA network was constructed using mutual DEmiRNAs in two interaction networks as nodes. mRNAs validated as significantly overexpressed in RCC by Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and quantitative polymerase chain reaction (q-PCR), along with the correlative miRNAs, were used for survival analysis. Finally, a ceRNA network with 13 upregulated circRNAs, 8 downregulated miRNAs and 21 upregulated mRNAs was constructed, in which Anti-Silencing Function 1B Histone Chaperone (ASF1B) and Forkhead Box M1 (FOXM1) were considered significant by Oncomine, GEPIA and q-PCR. Survival analysis showed that ASF1B, FOXM1 and hsa_miR_1254 were significantly negatively correlated but hsa_miR_129-5p was positively correlated with overall survival time. Exploration of the ceRNA network revealed the prognostic hsa_circ_0002024/hsa_miR_129-5p/ASF1B axis. Therefore, hsa_circ_0002024 was identified as a prognostic ceRNA that might sponge hsa_miR_129-5p to regulate ASF1B and affect RCC prognosis. However, further validation is needed.