Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome

Abstract

Accumulating evidence suggests that circular RNAs (circRNAs)—miRNA–mRNA ceRNA regulatory network—may play an important role in neurological disorders, such as Alzheimer’s disease (AD). Interestingly, neuropathological changes that closely resemble AD have been found in nearly all Down syndrome (DS) cases > 35 years. However, few studies have reported circRNA transcriptional profiling in DS cases, which is caused by a chromosomal aberration of trisomy 21. Here, we characterized the expression profiles of circRNAs in the fetal hippocampus of DS patients (n = 8) and controls (n = 6) by using microarray. MiRNA, mRNA expression profiling of DS from our previous study and scRNA-seq data describing normal fetal hippocampus development (GEO) were also integrated into the analysis. The similarity between circRNAs/genes with traits/cell-types was calculated by weighted correlation network analysis (WGCNA). miRanda and miRWalk2 were used to predict ceRNA network interactions. We identified a total of 7,078 significantly differentially expressed (DE) circRNAs, including 2,637 upregulated and 4,441 downregulated genes, respectively. WGCNA obtained 15 hub circRNAs and 6 modules with cell type–specific expression patterns among scRNA-seq data. Finally, a core ceRNA network was constructed by 14 hub circRNAs, 17 DE miRNA targets and 245 DE mRNA targets with a cell type–specific expression pattern annotation. Known functional molecules in DS or neurodegeneration (e.g., miR-138, OLIG1, and TPM2) were also included in this network. Our findings are the first to delineate the landscape of circRNAs in DS and the first to effectively integrate ceRNA regulation with scRNA-seq data. These data may provide a valuable resource for further research on the molecular mechanisms or therapeutic targets underlying DS neuropathy.

Identification of the Similarities and Differences of Molecular Networks Associated With Fear Memory Formation, Extinction, and Updating in the Amygdala

“…Finally, circRNA-miRNA-mRNA networks in different memory stages were established according to ceRNA theory. Dysfunctional circRNA-miRNA-mRNA regulatory networks represent an essential layer of epigenetic control in central nervous system disorders (Wang et al, 2020 ). Given the bioinformatics analysis results and ceRNA networks, our study identified 14 circRNAs, 2 miRNAs, and 4 mRNAs involved in memory extinction and retrieval-extinction in mice, which constituted 2 ceRNA networks.…”

Functional Role of circRNAs in the Regulation of Fetal Development, Muscle Development, and Lactation in Livestock

“…Dang et al studied human embryonic development and found that there were 1,032 types of circRNAs in the exon region of 2,974 genes in cells (endocell clusters, nourishing ectoderm cells, etc.) at different developmental stages [15]. Most circRNAs can perform specific dynamic regulation during embryonic development and are mainly involved in the regulation of material metabolic pathways in early embryonic development [15].…”

“…at different developmental stages [15]. Most circRNAs can perform specific dynamic regulation during embryonic development and are mainly involved in the regulation of material metabolic pathways in early embryonic development [15]. 3 BioMed Research International detect the expression of circRNAs [14].…”

“…In addition, studies have shown that circRNAs can regulate fetal development, and their expression is the most abundant and complex in the cerebral cortex on the 60th day of pregnancy [14][15][16]. Studies have shown that there are 10,032 circRNAs in human ocytes and embryos, a small portion of which are maternally expressed, and most of the circRNAs have been shown to be related to animal embryo development [17].…”

Multiple-microarray analysis for identification of key genes involved in diabetic nephropathy

“…[6] With the development of gene expression profiles, bioinformatics have become most common used strategies to screen key biomarkers in a variety of diseases including DN. [1,7,8] TGFβ1 is reported to be differentially expressed in DN and may participate in the development of DN. [9] Xu et al find hub genes associated with DN using data, and identify 13 hub genes including C3, FN1, COL1A2, LUM, THBS2, CD44, LYZ, FOS, EGR1, ALB, PLG, EGF, and DUSP1.…”