Identification of Functional CircRNA–miRNA–mRNA Regulatory Network in Dorsolateral Prefrontal Cortex Neurons of Patients With Cocaine Use Disorder

Abstract

Increasing evidence has indicated that circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) regulatory network to regulate the expression of target genes by sponging microRNAs (miRNAs), and therefore play an essential role in many neuropsychiatric disorders, including cocaine use disorder. However, the functional roles and regulatory mechanisms of circRNAs as ceRNAs in dorsolateral prefrontal cortex (dlPFC) of patients with cocaine use disorder remain to be determined. In this study, an expression profiling for dlPFC in 19 patients with cocaine use disorder and 17 controls from Gene Expression Omnibus datasets was used for the differentially expressed circRNAs analysis and the differentially expressed mRNAs analysis. Several tools were used to predict the miRNAs targeted by the circRNAs and the miRNAs targeted mRNAs, which then overlapped with the cocaine-associated differentially expressed mRNAs to determine the functional roles of circRNAs. Functional analysis for the obtained mRNAs was performed via Gene Ontology (GO) in Metascape database. Integrated bioinformatics analysis was conducted to further characterize the circRNA–miRNA–mRNA regulatory network and identify the functions of distinct circRNAs. We found a total of 41 differentially expressed circRNAs, and 98 miRNAs were targeted by these circRNAs. The overlapped mRNAs targeted by the miRNAs and the differentially expressed mRNAs constructed a circRNA–miRNA–mRNA regulation network including 24 circRNAs, 43 miRNAs, and 82 mRNAs in the dlPFC of patients with cocaine use disorder. Functional analysis indicated the regulation network mainly participated in cell response-related, receptor signaling-related, protein modification-related and axonogenesis-related pathways, which might be involved with cocaine use disorder. Additionally, we determined four hub genes (HSP90AA1, HSPA1B, YWHAG, and RAB8A) from the protein–protein interaction network and constructed a circRNA–miRNA-hub gene subnetwork based on the four hub genes. In conclusion, our findings provide a deeper understanding of the circRNAs-related ceRNAs regulatory mechanisms in the pathogenesis of cocaine use disorder.

Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer’s Disease Mice via Transcriptomic and Cellular Analysis

“…The downregulation of circRims1 has been observed in vascular dementia rats [ 58 ], while circZNF827 negatively regulates neuronal differentiation [ 59 ]. Finally, circGrin2b has been identified to be upregulated in the dorsolateral prefrontal cortex of patients with a cocaine use disorder [ 60 ].…”

AAGGG repeat expansions trigger RFC1-independent synaptic dysregulation in human CANVAS Neurons

“…Total rRNA-depleted RNA was extracted from 10-weekaged CANVAS patient and control iPSC-derived neurons and paired-end reads were processed and analyzed using packages described in methods. A known list of circRNA species [46][47][48][49][50] were detected at comparable levels in CANVAS and control samples (Figure 3B), however, no backspliced reads were identified to map to RFC1 intron 2 region or across the RFC1 transcript, indicating a lack of detectable circular RNA species deriving from the RFC1 locus (Figure 3B). the +0/+1/+2 reading frames.…”

CircRNAs: Roles in regulating head and neck squamous cell carcinoma

“…Cerebellar degeneration‐related protein 1 antisense RNA (CDR1as), also known as circular RNA sponge for miR-7 (ciRS-7), was reported to antagonize miR-7 availability ( 25 ). By targeting different miRNAs and mRNAs, circRNAs are involved in the pathogenesis of a variety of diseases, including neurological diseases ( 26 ), psychiatric diseases ( 27 ), autoimmune diseases ( 28 ), cardiovascular diseases ( 29 , 30 ), cartilage degenerative diseases ( 31 , 32 ), diabetes ( 33 , 34 ), pulmonary fibrosis ( 35 , 36 ), and various cancers ( 10 , 37 – 39 ).…”