Identification of Prostate Cancer-Related Circular RNA Through Bioinformatics Analysis

Abstract

Background: Prostate cancer (PCa) is one of the most common malignant tumors worldwide. Accumulating evidence has suggested that circular RNAs (circRNAs) are involved in the development and progression of various cancers, and they show great potential as novel biomarkers. However, the underlying mechanisms and specific functions of most circRNAs in PCa remain unknown. Here, we aimed to identify circRNAs with potential roles in PCa from the PCa expression profile. Methods: We used data downloaded from the Gene Expression Omnibus to identify circRNAs that were differentially expressed between PCa samples and adjacent nontumor samples. Relative expression levels of identified circRNAs were validated by quantitative real-time PCR. Micro (mi)RNA response elements were predicted by the CircInteractome database, and miRNA target genes were predicted by miRDB, miRTarBase, and TargetScan databases. Gene ontology (GO) enrichment analysis and pathway analysis revealed the potential biological and functional roles of these target genes. A circRNA-miRNA-mRNA interaction network was constructed by Cytoscape. The interaction between circRNAs and miRNAs in PCa was thoroughly reviewed in the PubMed. Finally, the mRNA expression of these genes was validated by the Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The expression of proteins encoded by these genes was further validated by the Human protein Atlas (HPA) database. Results: A total of 60 circRNAs that were differentially expressed between PCa and healthy samples were screened, of which 15 were annotated. Three circRNAs (hsa_circ_0024353, hsa_circ_0085494, hsa_circ_0031408) certified the criteria were studied. The results of quantitative real-time PCR demonstrated that the expression of hsa_circ_0024353 was significantly downregulated in PC-3 cells when compared with RWPE-1 cells, while the expression of hsa_circ_0031408 and hsa_circ_0085494 was significantly upregulated in PC-3 cells when compared with RWPE-1 cells. GO and Kyoto Encyclopedia of Genes and Genomes analyses found that target genes were mainly enriched in metabolic processes and pathways involving phosphoinositide 3-kinase-Akt signaling, hypoxia-inducible factor-1 signaling, p53 signaling, and the cell cycle. A total of 11 miRNA target genes showing differential expression between

Identification of Potential Genomic Alterations and the circRNA-miRNA-mRNA Regulatory Network in Primary and Recurrent Synovial Sarcomas

“…Genes can be targeted to identify upstream miRNAs. A total of 10 miRNAs were identified in this study, with studies finding hsa-let-7f-2-3p to be associated with bladder cancer progression (He et al, 2018), hsa-mir-1244 (Li et al, 2017) and hsa-mir-1197 (Yang et al, 2020) to be associated with lung cancer, and hsa-mir-1253 (Wu et al, 2020) to be associated with prostate cancer, and other miRNAs not found to be associated with cancer. It has been established that circRNA can function as "sponges" to recruit the corresponding miRNAs by interacting with miRNA binding sites, thereby playing an indirect role in regulating gene expression (Bai et al, 2020).…”

Silencing of circDPP4 suppresses cell progression of human prostate cancer and enhances docetaxel cytotoxicity through regulating the miR‐564/ZIC2 axis

“…CircRNAs are widespread functional RNAs that promote or suppress the progression of PC, 14 and multiple abnormally expressed circRNAs have been identified to be PC‐related 22,26,27 . Pro‐oncogenic circRNAs such as hsa_circ_0000735 and anti‐oncogenic circRNA such as circFOXO3 are connected with the progression of PC, as well as DTX resistance 28,29 .…”

“…CircRNAs could act as miRNA sponges through a competitive endogenous RNA (ceRNA) network to master the expression of target mRNAs 22,23 . The present study aimed to investigate the expression and role of circDPP4 in cell progression of PC cells both in vitro and in vivo and DTX cytotoxicity in vitro .…”

Circular RNAs in prostate cancer: Biogenesis, biological functions, and clinical significance

“…identified 60 circRNAs differentially expressed between PCa tissues and normal tissues, and used bioinformatics to predict three circRNA-miRNA-mRNA interaction axes. 62 …”

“…Using the GSE140927 dataset, Wu et al identified 60 circRNAs differentially expressed between PCa tissues and normal tissues, and used bioinformatics to predict three circRNA-miRNA-mRNA interaction axes. 62 In general, there are a large number of aberrantly expressed circRNAs between PCa tissues and normal tissues. In most studies, the number of circRNAs downregulated was higher than those upregulated.…”