Gray Lachlan G, Mills James D, Curry-Hyde Ashton, Devore Sasha, Friedman Daniel, Thom Maria, Scott Catherine, Thijs Roland D, Aronica Eleonora, Devinsky Orrin, Janitz Michael
School of Biotechnology and Biomolecular Sciences, University of New South Wales Sydney, Sydney, NSW, Australia.
Amsterdam UMC, Department of (Neuro)Pathology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands.
Front Genet. 2020 Sep 25;11:564301. doi: 10.3389/fgene.2020.564301. eCollection 2020.
Circular RNAs (circRNAs) regulate mRNA translation by binding to microRNAs (miRNAs), and their expression is altered in diverse disorders, including cancer, cardiovascular disease, and Parkinson's disease. Here, we compare circRNA expression patterns in the temporal cortex and hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and healthy controls. Nine circRNAs showed significant differential expression, including circRNA-, which is expressed in synapses. Further, we identified miRNA binding sites within the sequences of differentially expressed (DE) circRNAs; expression levels of mRNAs correlated with changes in complementary miRNAs. Gene set enrichment analysis of mRNA targets revealed functions in heterocyclic compound binding, regulation of transcription, and signal transduction, which maintain the structure and function of hippocampal neurons. The circRNA-miRNA-mRNA interaction networks illuminate the molecular changes in MTLE, which may be pathogenic or an effect of the disease or treatments and suggests that DE circRNAs and associated miRNAs may be novel therapeutic targets.
环状RNA（circRNAs）通过与微小RNA（miRNAs）结合来调节mRNA翻译，并且它们的表达在多种疾病中发生改变，包括癌症、心血管疾病和帕金森病。在此，我们比较了药物难治性内侧颞叶癫痫（MTLE）患者与健康对照者颞叶皮质和海马中的circRNA表达模式。9种circRNAs表现出显著差异表达，包括在突触中表达的circRNA-。此外，我们在差异表达（DE）circRNAs的序列中鉴定出miRNA结合位点；mRNA的表达水平与互补miRNAs的变化相关。对mRNA靶标的基因集富集分析揭示了在杂环化合物结合、转录调控和信号转导中的功能，这些功能维持海马神经元的结构和功能。circRNA-miRNA-mRNA相互作用网络阐明了MTLE中的分子变化，这些变化可能是致病性的，或是疾病或治疗的结果，并表明DE circRNAs和相关miRNAs可能是新的治疗靶点。
