AUTHOR=Chen Yun , Li Xianfeng , Meng Shiqiu , Huang Shihao , Chang Suhua , Shi Jie 

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

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 15 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.839233

DOI=10.3389/fnmol.2022.839233

ISSN=1662-5099

ABSTRACT=Increasing evidence has indicated that circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) regulatory networks to regulate the expression of target genes by sponging 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. The miRNAs targeted by the circRNAs and the miRNAs targeted mRNAs were predicted by integrating several tools, which further overlapped with the cocaine-associated differentially expressed mRNAs to get functional roles of circRNAs. Functional analysis for the obtained mRNAs was performed via Gene Ontology 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 4 hub genes. In conclusion, our findings provide a deeper understanding of the circRNA-related ceRNA regulatory mechanisms in the pathogenesis of cocaine use disorder.