Integrating circRNAs-miRNAs-mRNAs into ceRNAs network explores core regulatory mechanisms in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a common and complexhereditary nephropathy. Although most patients develop symptoms after adults, theybegin to bud in their fetal period. However, the underlying molecular mechanism andexact cause of ADPKD remain elusive. Therefore, based on the expression profile data ofperipheral blood from 3 patients with ADPKD and 3 normal controls sequenced byHuman Clariom D Array Chip, the core regulatory mechanism was explored with thecomprehensive circRNAs-miRNAs-mRNAs molecular target network analysis. In viewof the interaction mechanism of ceRNAs, we performed circRNAs-miRNAs targeting andtarget gene prediction for ADPKD-associated miRNAs, and identified interactionrelationship between 29 differential miRNAs and both 17 differential circRNAs and 1665differential mRNAs. These target genes are significantly involved in cell-matrix adhesionand deposition, organ morphogenesis, inflammation and other related biological processesand cellular components such as phagocytic vesicles, cytoplasmic vesicles, and renalcyst-associated biological signal pathways (eg, Hippo signaling pathway). Then, based onthe transcription and post-transcriptional regulation of circRNAs-target and RNA-relatedinteractions, significant regulators of the circRNAs-miRNAs-mRNAs molecular targetnetwork were identified as core regulators, including 5 circRNAs, 22 miRNAs, with GOand KEGG pathways Enrichment results demonstrating that critical circRNAssignificantly enriched the biological progress associated with organ fibrosis, renal injury,and cystic kidney disease. The key circRNAs compete with miRNAs as ceRNAs toachieve the regulation of miRNAs target gene expression levels to affect theADPKD-related genes and ultimately regulate its pathogenesis. Overall, our workdeciphers a network of circRNAs-miRNAs-mRNAs molecular targets for ADPKDhelping to reveal the core regulatory mechanisms of this disease and to increase ourunderstanding of its underlying molecular mechanisms.