Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice
Background and Aims: Methionine has been proven to inhibit addictive behaviors of cocaine dependence. This study aimed to identify the potential mechanisms of MET relating to its inhibitory effects on cocaine induced cellular and behavioral changes.Methods: MRNA and miRNA high-throughput sequencing...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1076156/full |
| _version_ | 1797948134365593600 |
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| author | Yan Wang Yan Wang Lvyu Yang Lvyu Yang Hansheng Zhou Kunlin Zhang Mei Zhao Mei Zhao |
| author_facet | Yan Wang Yan Wang Lvyu Yang Lvyu Yang Hansheng Zhou Kunlin Zhang Mei Zhao Mei Zhao |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Background and Aims: Methionine has been proven to inhibit addictive behaviors of cocaine dependence. This study aimed to identify the potential mechanisms of MET relating to its inhibitory effects on cocaine induced cellular and behavioral changes.Methods: MRNA and miRNA high-throughput sequencing of the prefrontal cortex in a mouse model of cocaine conditioned place preference (CPP) combined with L-methionine was performed. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) regulated by cocaine and inhibited by L-methionine were identified. DEGs were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then, the identified DEGs were subjected to the DAVID webserver for functional annotation. Finally, miRNA-mRNA regulatory network and miRNA-mRNA-TF regulatory networks were established to screen key DE-miRNAs and coregulation network in Cytoscape.Results: Sequencing data analysis showed that L-methionine reversely regulated genes and miRNAs affected by cocaine. Pathways associated with drug addiction only enriched in CS-down with MC-up genes targeted by DE-miRNAs including GABAergic synapse, Glutamatergic synapse, Circadian entrainment, Axon guidance and Calcium signaling pathway. Drug addiction associated network was formed of 22 DEGs including calcium channel (Cacna1c, Cacna1e, Cacna1g and Cacng8), ephrin receptor genes (Ephb6 and Epha8) and ryanodine receptor genes (Ryr1 and Ryr2). Calcium channel gene network were identified as a core gene network modulated by L-methionine in response to cocaine dependence. Moreover, it was predicted that Grin1 and Fosb presented in TF-miRNA-mRNA coregulation network with a high degree of interaction as hub genes and interacted calcium channels.Conclusion: These identified key genes, miRNA and coregulation network demonstrated the efficacy of L-methionine in counteracting the effects of cocaine CPP. To a certain degree, it may provide some hints to better understand the underlying mechanism on L-methionine in response to cocaine abuse. |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T21:38:36Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-e2d058a1a40347dcb263cb17aac968d62023-01-19T07:44:33ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10761561076156Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in miceYan Wang0Yan Wang1Lvyu Yang2Lvyu Yang3Hansheng Zhou4Kunlin Zhang5Mei Zhao6Mei Zhao7CAS Key Lab of Mental Health, Institute of Psychology, Beijing, ChinaDepartment of psychology, University of Chinese Academy of Sciences, Beijing, ChinaCAS Key Lab of Mental Health, Institute of Psychology, Beijing, ChinaDepartment of psychology, University of Chinese Academy of Sciences, Beijing, ChinaDepartment of Pharmacy, Linyi People’s Hospital, Linyi, Shandong Province, ChinaCAS Key Lab of Mental Health, Institute of Psychology, Beijing, ChinaCAS Key Lab of Mental Health, Institute of Psychology, Beijing, ChinaDepartment of psychology, University of Chinese Academy of Sciences, Beijing, ChinaBackground and Aims: Methionine has been proven to inhibit addictive behaviors of cocaine dependence. This study aimed to identify the potential mechanisms of MET relating to its inhibitory effects on cocaine induced cellular and behavioral changes.Methods: MRNA and miRNA high-throughput sequencing of the prefrontal cortex in a mouse model of cocaine conditioned place preference (CPP) combined with L-methionine was performed. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) regulated by cocaine and inhibited by L-methionine were identified. DEGs were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then, the identified DEGs were subjected to the DAVID webserver for functional annotation. Finally, miRNA-mRNA regulatory network and miRNA-mRNA-TF regulatory networks were established to screen key DE-miRNAs and coregulation network in Cytoscape.Results: Sequencing data analysis showed that L-methionine reversely regulated genes and miRNAs affected by cocaine. Pathways associated with drug addiction only enriched in CS-down with MC-up genes targeted by DE-miRNAs including GABAergic synapse, Glutamatergic synapse, Circadian entrainment, Axon guidance and Calcium signaling pathway. Drug addiction associated network was formed of 22 DEGs including calcium channel (Cacna1c, Cacna1e, Cacna1g and Cacng8), ephrin receptor genes (Ephb6 and Epha8) and ryanodine receptor genes (Ryr1 and Ryr2). Calcium channel gene network were identified as a core gene network modulated by L-methionine in response to cocaine dependence. Moreover, it was predicted that Grin1 and Fosb presented in TF-miRNA-mRNA coregulation network with a high degree of interaction as hub genes and interacted calcium channels.Conclusion: These identified key genes, miRNA and coregulation network demonstrated the efficacy of L-methionine in counteracting the effects of cocaine CPP. To a certain degree, it may provide some hints to better understand the underlying mechanism on L-methionine in response to cocaine abuse.https://www.frontiersin.org/articles/10.3389/fgene.2022.1076156/fullhigh-throughput sequencingmicroRNAgene expressionaddictionregulatory networkL-methionine |
| spellingShingle | Yan Wang Yan Wang Lvyu Yang Lvyu Yang Hansheng Zhou Kunlin Zhang Mei Zhao Mei Zhao Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice Frontiers in Genetics high-throughput sequencing microRNA gene expression addiction regulatory network L-methionine |
| title | Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice |
| title_full | Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice |
| title_fullStr | Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice |
| title_full_unstemmed | Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice |
| title_short | Identification of miRNA-mediated gene regulatory networks in L-methionine exposure counteracts cocaine-conditioned place preference in mice |
| title_sort | identification of mirna mediated gene regulatory networks in l methionine exposure counteracts cocaine conditioned place preference in mice |
| topic | high-throughput sequencing microRNA gene expression addiction regulatory network L-methionine |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1076156/full |
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