Dataset Information

Differential Methylation of CircRNA m6A in the APP/PS1 Alzheimer's Disease Mouse Model [cirRNA-seq]

ABSTRACT: Alzheimer's disease (AD) is a chronic neurological disease which characterized as memory loss and progressive cognitive impairment. The characteristic of AD pathologies include extracellular senile plaques formed by β-amyloid protein deposition, neurofifibrillary tangles formed byhyper-phosphorylation of tau protein, and neuronal loss caused by glial cell proliferation. However, the pathogenesis of AD is still unclear. Resent research have shown that the dysregulation of RNA methylation is related to many biological processes, including neurodevelopment and neurodegenerative diseases. N6-methyladenosine (m6A) is the mainly modification in eukaryotic RNA, and it may be associated with the pathophysiology of AD. Circular RNA (circRNA) is a new type of evolutionarily conserved non-coding RNA without 5’cap and 3’polyadenylic acid tail. Recent studies suggested that circRNA may involved in the pathogenesis of AD. m6A RNA methylation is also found in circRNAs. In this study, we performed high-throughput sequencing on the degree of circRNA m6A methylation in APP/PS1 AD and C57BL/6 mice. The results suggest that circRNA m6A methylation degree in AD mice is different compared to the control group. In addition, using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to predict related pathways, the results showed that the genes with different circRNA m6A methylation in AD mice is associated with axon guidance, long-term potentiation, glutama tergic synapse, cholinergic synapse, gabaergic synapse and long-term depression. The MeRIP-qPCR results showed that among the 8 selected circRNA m6A genes, there are 5 genes with increased methylation and others with decreased methylation. In summary, the results of this study indicate that circRNA m6A methylation may related to the pathogenesis of AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE216901 | GEO | 2022/11/03

REPOSITORIES: GEO

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Project description:Abstract Background: Cerebral ischemia-reperfusion (I/R) frequently caused the late-onset neuronal damage. Breviscapine has a promote in autophagy of microvascular endothelial cells in I/R and it can inhibit the oxidative damage and apoptosis. However, the mediation mechanism of breviscapine on neuronal cell death is unclear. Methods: Firstly, transcriptome sequencing was performed on three groups of mice neuronal normal group (Control group), oxygen-glucose deprivation/reoxygenation group (OGD/R group) and breviscapine administration group (Therapy group). Differentially expressed genes (DEGs) between OGD/R and Control groups, and between Therapy and OGD/R groups were obtained by limma package. The N6-methyladenosine (m6A) methylation related DEGs were selected out by the Pearson correlation analysis. Then, prediction and confirmation of drug targets were performed by Swiss Target Prediction and UniProt Knowledgebase (UniProtKB) datebase, and key genes were obtained by Pearson correlation analysis between m6A-related DEGs and drug target genes. Next, gene set enrichment (GSEA) analysis and Ingenuity pathway analysis (IPA) were used to obtain the pathways of key genes. Finally, a circRNA-miRNA-mRNA network was constructed based on the mRNAs, circRNAs and miRNAs. Results: 2250 DEGs between OGD/R and Control groups and 757 DEGs between Therapy and OGD/R groups were selected out by differential analysis. A total of 7 m6A related DEGs including Arl4d, Gm10653, Gm1113, Kcns3, Olfml2a, Stk26 and Tfcp2l1 were obtained by Pearson correlation analysis. Four key genes (Tfcp2l1, Kcns3, Olfml2a and Arl4d) were acquired, and GSEA showed that these key genes were significantly participated in DNA repair, e2f targets and g2m checkpoint. IPA revealed that Tfcp2l1 played a significant role in human embryonic stem cell pluripotency. The circRNA-miRNA-mRNA network showed that the mmu_circ_0001258 regulated the Tfcp2l1 by mmu-miR-301b-3p. Conclusions: In conclusion, four key genes including Tfcp2l1, Kcns3, Olfml2a and Arl4d significantly associated with the treatment of OGD/R by breviscapine were acquired, which would provide a theoretical basis for clinical trials.

Dataset Information

Differential Methylation of CircRNA m6A in the APP/PS1 Alzheimer's Disease Mouse Model [cirRNA-seq]

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