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Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods

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机构: [1]Department of Interventional Radiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China. [2]Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China. [3]Department of Organ Transplantation Centre, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China
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关键词: Cerebral ischaemia-reperfusion Breviscapine m6A Bioinformatics methods

摘要:
Cerebral ischaemia‒reperfusion (I/R) frequently causes late-onset neuronal damage. Breviscapine promotes autophagy in microvascular endothelial cells in I/R and can inhibit oxidative damage and apoptosis. However, the mediation mechanism of breviscapine on neuronal cell death is unclear.First, transcriptome sequencing was performed on three groups of mice: the neuronal normal group (Control group), the oxygen-glucose deprivation/ reoxygenation group (OGD/R group) and the breviscapine administration group (Therapy group). Differentially expressed genes (DEGs) between the OGD/R and control groups and between the Therapy and OGD/R groups were obtained by the limma package. N6-methyladenosine (m6A) methylation-related DEGs were selected by Pearson correlation analysis. Then, prediction and confirmation of drug targets were performed by Swiss Target Prediction and UniProt Knowledgebase (UniProtKB) database, and key genes were obtained by Pearson correlation analysis between m6A-related DEGs and drug target genes. Next, gene set enrichment analysis (GSEA) 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.A total of 2250 DEGs between the OGD/R and control groups and 757 DEGs between the Therapy and OGD/R groups were selected 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 significantly participated in DNA repair, e2f targets and the g2m checkpoint. IPA revealed that Tfcp2l1 played a significant role in human embryonic stem cell pluripotency. The circRNA-miRNA‒mRNA network showed that mmu_circ_0001258 regulated Tfcp2l1 by mmu-miR-301b-3p.In conclusion, four key genes, Tfcp2l1, Kcns3, Olfml2a and Arl4d, significantly associated with the treatment of OGD/R by breviscapine were identified, which provides a theoretical basis for clinical trials.© 2023. BioMed Central Ltd., part of Springer Nature.

基金:

基金编号: Grant Number: 202102AA100067] , Yunnan Provincial Clinical Medical Center for Neurological Diseases [Grant Number: ZX2019030501] and from Yunnan Provincial Department of Science and Technology - Kunming Medical University Applied Basic Research Joint Fund [Grant Number:202301AY070001-008

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大类 | 4 区 医学
小类 | 4 区 遗传学
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Q3 GENETICS & HEREDITY
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Q3 GENETICS & HEREDITY

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第一作者机构: [1]Department of Interventional Radiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
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