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
School of Medicine, IMPACT, Institute for Innovation in Physical and Mental health and Clinical Translation, Deakin University, Geelong, VIC, Australia.
Genomics Centre, School of Life and Environmental Sciences, Deakin University, Burwood, VIC, Australia.
Front Pharmacol. 2022 Apr 8;13:873271. doi: 10.3389/fphar.2022.873271. eCollection 2022.
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.
长链非编码RNA（lncRNAs）可能在包括双相情感障碍（BD）在内的精神疾病中发挥作用。我们研究了用广泛处方的BD药物处理的神经元样细胞中的mRNA-lncRNA共表达模式。目的是揭示BD药物复杂机制的见解，并突出新药开发的潜在靶点。将人神经元样（NT2-N）细胞用拉莫三嗪、锂盐、喹硫平、丙戊酸盐或溶剂处理24小时。对全基因组mRNA表达进行定量，用于加权基因共表达网络分析（WGCNA），以将mRNA的表达水平与lncRNAs相关联。对与药物反应相关的关键共表达模块进行功能富集分析和枢纽lncRNA鉴定。我们构建了lncRNA-mRNA共表达网络，确定了这些治疗方法背后的关键模块及其丰富的生物学功能。关键模块中富集的过程包括突触小泡循环、内质网相关功能和神经发育。几种lncRNAs，如 和 ，被突出显示为关键模块的驱动基因。我们的研究证明了lncRNAs在BD药物作用机制中的关键作用。几种lncRNAs已被认为是药物作用的主要调节因子，作为治疗BD的新型药物靶点值得进一步研究。
