Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods
Abstract Background 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-023-01651-3 |
| _version_ | 1797451145773318144 |
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| author | Cheng Wan Jingchun Pei Dan Wang Jihong Hu Zhiwei Tang Wei Zhao |
| author_facet | Cheng Wan Jingchun Pei Dan Wang Jihong Hu Zhiwei Tang Wei Zhao |
| author_sort | Cheng Wan |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-03-09T14:50:35Z |
| format | Article |
| id | doaj.art-a9c9dcec320a41d9abe7327cafd5f450 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-09T14:50:35Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-a9c9dcec320a41d9abe7327cafd5f4502023-11-26T14:30:24ZengBMCBMC Medical Genomics1755-87942023-09-0116111310.1186/s12920-023-01651-3Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methodsCheng Wan0Jingchun Pei1Dan Wang2Jihong Hu3Zhiwei Tang4Wei Zhao5Department of Interventional Radiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Organ Transplantation Centre, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Interventional Radiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Interventional Radiology, The First Affiliated Hospital of Kunming Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12920-023-01651-3Cerebral ischaemia-reperfusionBreviscapinem6ABioinformatics methods |
| spellingShingle | Cheng Wan Jingchun Pei Dan Wang Jihong Hu Zhiwei Tang Wei Zhao Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods BMC Medical Genomics Cerebral ischaemia-reperfusion Breviscapine m6A Bioinformatics methods |
| title | Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods |
| title_full | Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods |
| title_fullStr | Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods |
| title_full_unstemmed | Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods |
| title_short | Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods |
| title_sort | identification of m6a methylation related genes in cerebral ischaemia reperfusion of breviscapus therapy based on bioinformatics methods |
| topic | Cerebral ischaemia-reperfusion Breviscapine m6A Bioinformatics methods |
| url | https://doi.org/10.1186/s12920-023-01651-3 |
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