Profiling circular RNA in methamphetamine-treated primary cortical neurons identified novel circRNAs related to methamphetamine addiction

Li, Junwei; Shi, Qingqing; Wang, Qian; Tan, Xu; Pang, Kunkun; Liu, Xiaoyu; Zhu, Shirley; Xi, Kaiyan; Zhang, Jing; Gao, Qing; Hu, Yaomin; Sun, Jinhao

doi:10.1016/j.neulet.2019.02.032

Cited by 27 publications

(12 citation statements)

References 33 publications

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“…The existing literature on drug-induced circRNA expression has reported circRNA regulation in primary cortical neurons and the cerebellum in response to methamphetamine treatment, and in the striatum in response to cocaine self-administration [54][55][56]. None of the five heroin-associated circRNAs validated in the present study were regulated by psychostimulants in the aforementioned studies.…”

Section: Discussionsupporting

confidence: 41%

Heroin Regulates Orbitofrontal Circular RNAs

Floris

Gillespie

Zanda

et al. 2022

IJMS

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The number of drug overdose deaths involving opioids continues to rise in the United States. Many patients with opioid use disorder (OUD) that seek treatment still experience relapse. Perseverant opioid seeking behaviors represent a major challenge to treating OUD and additional therapeutic development will require insight into opioid-induced neurobiological adaptations. In this study, we explored the regulation of a novel class of RNAs, circular RNAs (circRNAs), by the addictive opioid heroin in the rat orbitofrontal cortex (OFC), a brain region that mediates behavioral responses to rewarding stimuli. Microarray analysis identified 76 OFC circRNAs significantly regulated in male rats after heroin self-administration. We evaluated the specificity of these findings by measuring heroin-associated circRNA expression in female rats after heroin self-administration and in rats that self-administered sucrose. We identify circGrin2b, circUbe2cp, circAnks1a, circAdcy5 and circSlc24A2 as heroin-responsive circRNAs in the OFC. Linear mRNA levels of heroin-associated circRNAs were unchanged except for Grin2b and Adcy5. An integrated bioinformatics analysis of regulated circRNAs identified microRNAs predicted to bind heroin-associated circRNAs and downstream targets of circRNA: microRNA sponging. Thus, heroin regulates the expression of OFC RNA splice variants that circularize and may impact cellular processes that contribute to the neurobiological adaptations that arise from chronic heroin exposure.

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Section: Discussionsupporting

confidence: 41%

Heroin Regulates Orbitofrontal Circular RNAs

Floris

Gillespie

Zanda

et al. 2022

IJMS

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“…To investigate the potential functions of DE-circRNAs, we also constructed a circRNA-miRNA-mRNA interaction ceRNA network, which included six circRNAs, 13 miRNAs, and 112 mRNAs. Previous studies have established that circRNAs might function as microRNA sponges, inducing target mRNA silencing, thereby regulating gene expression at the post-transcriptional level [13][14][15][16][17]. Herein, through an in silico analysis, we predict that mmu-circRNA-0003292 is a sponge of miRNA-132.…”

Section: Discussionmentioning

confidence: 90%

“…Recent studies have shown that many circRNAs play important roles in the regulation of gene expression at both transcriptional and post-transcriptional levels, and in the pathogenesis and progression of neurodegenerative diseases [13][14][15][16][17]. For example, circRNAs are abundantly expressed in the central nervous system, and play an important role in striatal synaptic plasticity and neuronal dysfunction [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Profiling of Circular RNA in Different Brain Regions of Parkinson’s Disease in a Mouse Model

Jia

Zhou

Liu

et al. 2020

IJMS

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Parkinson’s disease (PD) is the second most common neurodegenerative disease and although many studies have been done on this disease, the underlying mechanisms are still poorly understood and further studies are warranted. Therefore, this study identified circRNA expression profiles in the cerebral cortex (CC), hippocampus (HP), striatum (ST), and cerebellum (CB) regions of the 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model using RNA sequencing (RNA-seq), and differentially expressed circRNA were validated using reverse transcription quantitative real-time PCR (qRT-PCR). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analyses were also performed to explore the potential function of circRNAs. The results show that, compared with the control group, 24, 66, 71, and 121 differentially expressed circRNAs (DE-circRNAs) were found in the CC, HP, ST, and CB, respectively. PDST vs. PDCB, PDST vs. PDHP, and PDCB vs. PDHP groups have 578, 110, and 749 DE-circRNAs, respectively. Then, seven DE-cirRNAs were selected for qRT-PCR verification, where the expressions were consistent with the sequencing analysis. The GO and KEGG pathway analyses revealed that these DE-circRNAs participate in several biological functions and signaling pathways, including glutamic synapse, neuron to neuron synapse, cell morphogenesis involved in neuron differentiation, Parkinson’s disease, axon guidance, cGMP-PKG signaling pathway, and PI3K-Akt signaling pathway. Furthermore, the KEGG analysis of the target genes predicted by DE-circRNAs indicated that the target genes predicted by mmu_circRNA_0003292, mmu_circRNA_0001320, mmu_circRNA_0005976, and mmu_circRNA_0005388 were involved in the PD-related pathway. Overall, this is the first study on the expression profile of circRNAs in the different brain regions of PD mouse model. These results might facilitate our understanding of the potential roles of circRNAs in the pathogenesis of PD. Moreover, the results also indicate that the mmu_circRNA_0003292-miRNA-132-Nr4a2 pathway might be involved in the regulation of the molecular mechanism of Parkinson’s disease.

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“…Circular RNAs are endogenous non-coding RNAs with widespread distribution and various cellular function ( Hansen et al, 2013 ; Vicens and Westhof, 2014 ; Rybak-Wolf et al, 2015 ; Du et al, 2017 ; Greene et al, 2017 ; Li et al, 2018 ; Mehta et al, 2020 ). Numerous studies have shown that circRNAs have an important influence on many complicated neuropsychiatric disorders ( Cui et al, 2016 ; Zhang et al, 2018 ; An et al, 2019 ; Liu et al, 2019 ; Mahmoudi et al, 2019 ; Huang et al, 2020 ; Zhang Y. et al, 2020 ; Zimmerman et al, 2020 ), including drug addiction ( Huang et al, 2017 ; Bu et al, 2019 ; Li et al, 2019 , 2020 ; Zhang H. et al, 2020 ). Knockdown of circHomer1 ameliorates methamphetamine-induced neuronal injury through inhibiting Bbc3 expression ( Li et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Meng

et al. 2022

Front. Mol. Neurosci.

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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.

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Profiling circular RNA in methamphetamine-treated primary cortical neurons identified novel circRNAs related to methamphetamine addiction

Cited by 27 publications

References 33 publications

Heroin Regulates Orbitofrontal Circular RNAs

Heroin Regulates Orbitofrontal Circular RNAs

Transcriptomic Profiling of Circular RNA in Different Brain Regions of Parkinson’s Disease in a Mouse Model

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

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