liu-coexpressionnetworks-2022.pdf (1.97 MB)
Co-Expression Networks Unveiled Long Non-Coding RNAs as Molecular Targets of Drugs Used to Treat Bipolar Disorder
journal contribution
posted on 2022-04-01, 00:00 authored by Trang T T Truong, Chiara C Bortolasci, Briana Spolding, Bruna Panizzutti, Zoe LiuZoe Liu, Srisaiyini Kidnapillai, Mark Richardson, Laura Gray, Craig M Smith, Olivia M Dean, Jee Hyun Kim, Michael Berk, Ken WalderLong 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.
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Journal
Frontiers in PharmacologyVolume
13Article number
873271Pagination
1 - 12Publisher
Frontiers Media SALocation
Lausanne, SwitzerlandPublisher DOI
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1663-9812eISSN
1663-9812Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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