Cocaine induces differential circular RNA expression in striatum

Bu, Qian; Long, Hailei; Shao, Xue; Gu, Hui; Kong, Jueying; Luo, Li; Liu, Bin; Guo, Wei; Wang, Hongbo; Tian, Jingwei; Zhao, Yinglan; Cen, Xiaobo

doi:10.1038/s41398-019-0527-1

Cited by 29 publications

(18 citation statements)

References 52 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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“…The use of advanced annotation tools and deep sequencing of ribosomal RNA (rRNA)-depleted and RNase R-digested RNA samples has revealed the existence of tens of thousands of circRNAs ( Hansen et al, 2013 ; Memczak et al, 2013 ; Guo et al, 2014 ; Rybak-Wolf et al, 2014 ; You et al, 2015 ). Interestingly, circRNA expression has been shown to be altered in various psychiatric disorders ( Zimmerman et al, 2020 ), autism ( Chen et al, 2020 ), cocaine addiction ( Bu et al, 2019 ), and Alzheimer’s disease ( Dube et al, 2019 ). Among the potential functions of circRNAs are interactions with RBPs, sequestration of miRNAs, and transcriptional control of gene expression ( Hentze and Preiss, 2013 ; Barrett and Salzman, 2016 ; Gokool et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Prenatal Alcohol Exposure Results in Sex-Specific Alterations in Circular RNA Expression in the Developing Mouse Brain

et al. 2020

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Fetal alcohol spectrum disorders (FASD) are heterogeneous disorders associated with alcohol exposure to the developing fetus that are characterized by a range of adverse neurodevelopmental deficits. Despite the numerous genomics and genetic studies on FASD models, the comprehensive molecular understanding of the mechanisms that underlie FASD-related neurodevelopmental deficits remains elusive. Circular RNAs (circRNAs) are a subtype of long non-coding RNAs that are derived from back-splicing and covalent joining of exons and/or introns of protein-coding genes. Recent studies have shown that circRNAs are highly enriched in the brain, where they are developmentally regulated. However, the role of the majority of brain-enriched circRNAs in normal and pathological brain development and function has not been explored yet. Here we carried out the first systematic profiling of circRNA expression in response to prenatal alcohol exposure (PAE) in male and female embryonic day 18 (E18) whole brains. We observed that the changes in circRNA expression in response to PAE were notably sex-specific and that PAE tended to erase most of the sex-specificity in circRNA expression present in control (saccharin-treated) mice. On the other hand, RNA sequencing (RNA-seq) in the same samples showed that changes in protein-coding gene expression were not predominantly sex-specific. Using circRNA quantitative real-time PCR (qRT-PCR), we validated that circSatb2 , which is generated from the special AT-rich sequence-binding protein 2 ( Satb2 ) gene, is significantly upregulated in the brain of E18 male PAE mice. We also show that circPtchd2 , a circRNA synthesized from dispatched RND transporter family member 3 ( Disp3 , also known as Ptchd2 ), exhibits significantly higher expression in E18 control but not PAE female mouse brain relative to males. Taken together, our results demonstrate that PAE differentially alters circRNA expression in the developing brain in a sex-specific manner.

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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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Cocaine induces differential circular RNA expression in striatum

Cited by 29 publications

References 52 publications

Heroin Regulates Orbitofrontal Circular RNAs

Heroin Regulates Orbitofrontal Circular RNAs

Prenatal Alcohol Exposure Results in Sex-Specific Alterations in Circular RNA Expression in the Developing Mouse Brain

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

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