Construction and analysis of circular RNA molecular regulatory networks in clear cell renal cell carcinoma

Abstract

Increasing evidence has indicated that circular (circ)RNAs participate in carcinogenesis; however, the specific regulatory mechanisms underlying the effects of circRNAs, microRNAs (miRNAs/miRs) and genes on the development of clear cell renal cell carcinoma (CCRCC) remain unclear. In the present study, RNA microarray data from CCRCC tissues and control samples were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas, in order to identify significantly dysregulated circRNAs, miRNAs and genes. The Cancer-Specific circRNA Database was used to explore the interactions between miRNAs and circRNAs, whereas TargetScan and miRDB were employed to predict the mRNA targets of miRNAs. Functional enrichment and prognostic analyses were conducted in R. The results revealed that 324 circRNAs were downregulated, whereas 218 circRNAs were upregulated in cancer. In addition, a circRNA-miRNA-mRNA interaction network was constructed. Gene Ontology analysis of the upregulated genes revealed that these genes were enriched in biological processes, including ‘flavonoid metabolic process’, ‘cellular glucuronidation’ and ‘T cell activation’. The downregulated genes were mainly enriched in biological processes, such as ‘nephron development’, ‘kidney development’ and ‘renal system development’. The hub genes, including membrane palmitoylated protein 7, aldehyde dehydrogenase 6 family member A1, transcription factor AP-2α, collagen type IV α 4 chain, nuclear receptor subfamily 3 group C member 2, plasminogen, Holliday junction recognition protein, claudin 10, kinesin family member 18B and thyroid hormone receptor β, and the hub miRNAs, including miR-21-3p, miR-155-3p, miR-144-3p, miR-142-5p, miR-875-3p, miR-885-3p, miR-3941, miR-224-3p, miR-584-3p and miR-138-1-3p, were significantly associated with CCRCC survival. In conclusion, these results suggested that the significantly dysregulated circRNAs, miRNAs and genes identified in this study may be considered potential biomarkers of the carcinogenesis of CCRCC and the survival of patients with this disease.

Hsa_circ_0085576 promotes clear cell renal cell carcinoma tumorigenesis and metastasis through the miR-498/YAP1 axis

“…Many studies have demonstrated that circRNAs participate in the tumorigenesis of ccRCC [18][19][20]. However, to date, the functions of circRNAs in ccRCC remain largely unknown.…”

Circ-APBB1IP as a Prognostic Biomarker Promotes Clear Cell Renal Cell Carcinoma Progression Through The ERK1/2 Signaling Pathway

“…It is necessary to find novel biomarkers for reducing mortality rates [22]. With the development of genomic analysis platform, more and more circRNA have been identified, several studies have proved that circRNA was closely associated with ccRCC [23,24]. In this study, we aimed to investigate the biological roles and mechanisms of circ-APBB1IP in ccRCC development.…”

Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy

“…For instance, Ma et al found that 542 circRNAs were aberrantly expressed in clear cell RCC (ccRCC) by using a circRNA microarray. Among these, 324 circRNAs were significantly downregulated, whereas 218 were upregulated in ccRCC tumors [83]. Using the Arraystar microarray to profile seven matched ccRCC samples, Franz et al detected a total of 13,261 circRNAs, of which 78 circRNAs were upregulated and 91 were downregulated more than two-fold [84].…”