Systematic Characterization of Circular RNA-Associated CeRNA Network Identified Novel circRNA Biomarkers in Alzheimer's Disease

Alzheimer's disease (AD), a degenerative disease of the central nervous system, is the most common form of dementia in old age. The complexity and behavior of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) network remained poorly characterized in AD. The aim of this study was to elucidate the regulatory networks of dysregulated circRNAs from ceRNA view and identify potential risk circRNAs involved in AD pathogenesis. Consistent differentially expressed genes (CDEGs) were obtained using meta-analysis for multiple microarrays, and differentially expressed miRNAs (DEmiRs) were identified using empirical Bayes method. The circRNA-associated ceRNA network (cirCeNET) was constructed based on “ceRNA hypothesis” using an integrated system biology method. A total of 1,872 CDEGs and 48 DEmiRs were screened across different datasets. By mapping CDEGs and DEmiRs into the cirCeNET, an AD-related circRNA-associated ceRNA network (ADcirCeNET) was constructed, including 3,907 edges and 1,407 nodes (276 circRNAs, 14 miRNAs and 1,117 mRNAs). By prioritizing AD risk circRNA-associated ceRNAs, we found that the circRNA KIAA1586 occurred most frequently in the AD risk circRNA-associated ceRNAs and function as a ceRNA that operates by competitively binding three known AD-risk miRNAs. In silico functional analysis suggested that circRNA KIAA1586-related ceRNA network was significantly enriched in known AD-associated biological processes. Our study provided a global view and systematic dissection of circRNA-associated ceRNA network. The identified circRNA KIAA1586 may be a key risk factor involved in AD pathogenesis.