Co-Expression Networks Unveiled Long Non-Coding RNAs as Molecular Targets of Drugs Used to Treat Bipolar Disorder

Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medication...

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Published inFrontiers in pharmacology Vol. 13; p. 873271
Main Authors Truong, Trang TT, Bortolasci, Chiara C., Spolding, Briana, Panizzutti, Bruna, Liu, Zoe SJ, Kidnapillai, Srisaiyini, Richardson, Mark, Gray, Laura, Smith, Craig M., Dean, Olivia M., Kim, Jee Hyun, Berk, Michael, Walder, Ken
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 08.04.2022
Subjects
bipolar disorders
co-expression network
lncRNAs
mood stabilizers
Pharmacology
treatments
WGCNA
lncRNAs
mood disorders
bipolar disorders
mood stabilizers
WGCNA
treatments
co-expression network
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Abstract Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.
AbstractList Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.
Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.
Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.
Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as and were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.
Author Richardson, Mark
Dean, Olivia M.
Panizzutti, Bruna
Walder, Ken
Gray, Laura
Spolding, Briana
Liu, Zoe SJ
Berk, Michael
Truong, Trang TT
Kidnapillai, Srisaiyini
Kim, Jee Hyun
Bortolasci, Chiara C.
Smith, Craig M.
AuthorAffiliation 4 Orygen, The National Centre of Excellence in Youth Mental Health , Centre for Youth Mental Health , Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry , The University of Melbourne , Melbourne , VIC , Australia
3 The Florey Institute of Neuroscience and Mental Health , University of Melbourne , Parkville , VIC , Australia
1 School of Medicine , IMPACT , Institute for Innovation in Physical and Mental health and Clinical Translation , Deakin University , Geelong , VIC , Australia
2 Genomics Centre , School of Life and Environmental Sciences , Deakin University , Burwood , VIC , Australia
AuthorAffiliation_xml – name: 2 Genomics Centre , School of Life and Environmental Sciences , Deakin University , Burwood , VIC , Australia
– name: 1 School of Medicine , IMPACT , Institute for Innovation in Physical and Mental health and Clinical Translation , Deakin University , Geelong , VIC , Australia
– name: 3 The Florey Institute of Neuroscience and Mental Health , University of Melbourne , Parkville , VIC , Australia
– name: 4 Orygen, The National Centre of Excellence in Youth Mental Health , Centre for Youth Mental Health , Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry , The University of Melbourne , Melbourne , VIC , Australia
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Copyright Copyright © 2022 Truong, Bortolasci, Spolding, Panizzutti, Liu, Kidnapillai, Richardson, Gray, Smith, Dean, Kim, Berk and Walder.
Copyright © 2022 Truong, Bortolasci, Spolding, Panizzutti, Liu, Kidnapillai, Richardson, Gray, Smith, Dean, Kim, Berk and Walder. 2022 Truong, Bortolasci, Spolding, Panizzutti, Liu, Kidnapillai, Richardson, Gray, Smith, Dean, Kim, Berk and Walder
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Keywords lncRNAs
mood disorders
bipolar disorders
mood stabilizers
WGCNA
treatments
co-expression network
Language English
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Lu Jia, Capital Medical University, China
Edited by: Francisco Lopez-Munoz, Camilo José Cela University, Spain
This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology
Reviewed by: Lifeng Li, First Affiliated Hospital of Zhengzhou University, China
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Snippet Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in...
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SubjectTerms bipolar disorders
co-expression network
lncRNAs
mood stabilizers
Pharmacology
treatments
WGCNA
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Title Co-Expression Networks Unveiled Long Non-Coding RNAs as Molecular Targets of Drugs Used to Treat Bipolar Disorder
URI https://www.ncbi.nlm.nih.gov/pubmed/35462908
https://www.proquest.com/docview/2655102996
https://pubmed.ncbi.nlm.nih.gov/PMC9024411
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