Deregulation of ceRNA Networks in Frontal Cortex and Choroid Plexus of Brain during SARS‐CoV‐2 Infection Aggravates Neurological Manifestations: An Insight from Bulk and Single‐Cell Transcriptomic Analyses

下调和上调 竞争性内源性RNA 转录组 生物 脉络丛 马拉特1 小RNA 神经科学 细胞 细胞生物学 基因表达 基因 遗传学 长非编码RNA 中枢神经系统
作者
Deepyaman Das,Soumita Podder
出处
期刊:Advanced biology [Wiley]
卷期号:6 (8) 被引量:4
标识
DOI:10.1002/adbi.202101310
摘要

Although transcriptomic studies of SARS-CoV-2-infected brains have depicted variability in gene expression, the landscape of deregulated cell-specific regulatory circuits has not been elucidated yet. Hence, bulk and single-cell RNA-seq data are analyzed to gain detailed insights. Initially, two ceRNA networks with 19 and 3 differentially expressed (DE) hub lncRNAs are reconstructed in SARS-CoV-2 infected Frontal Cortex (FC) and Choroid Plexus (CP), respectively. Functional and pathway enrichment analyses of downstream mRNAs of deregulated ceRNA axes demonstrate impairment of neurological processes. Mapping of hub lncRNA-mRNA pairs from bulk RNA-seq with snRNA-seq data has indicated that NORAD, NEAT1, and STXBP5-AS1 are downregulated across 4, 4, and 2 FC cell types, respectively. At the same time, MIRLET7BHG and MALAT1 are upregulated in excitatory neurons of FC and neurons of CP, respectively. Here, it is hypothesized that downregulation of NORAD, NEAT1, and STXBP5-AS1, and upregulation of MIRLET7BHG and MALAT1 might deregulate respectively 51, 6, and 37, and 31 and 19 mRNAs in cell types of FC and CP. Afterward, 13 therapeutic miRNAs are traced that might safeguard against deregulated lncRNA-mRNA pairs of NORAD, NEAT1, and MIRLET7BHG in FC. This study helps to explain the plausible mechanism of post-COVID neurological manifestation and also to devise therapeutics against it.

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