m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms
BackgroundThe role of epigenetic modulation in immunity is receiving increased recognition—particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs)....
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.889141/full |
| _version_ | 1828294174479220736 |
|---|---|
| author | Aierpati Maimaiti Mirzat Turhon Mirzat Turhon Xiaojiang Cheng Riqing Su Kaheerman Kadeer Aximujiang Axier Dilimulati Ailaiti Yirizhati Aili Rena Abudusalamu Ajimu Kuerban Zengliang Wang Maimaitili Aisha |
| author_facet | Aierpati Maimaiti Mirzat Turhon Mirzat Turhon Xiaojiang Cheng Riqing Su Kaheerman Kadeer Aximujiang Axier Dilimulati Ailaiti Yirizhati Aili Rena Abudusalamu Ajimu Kuerban Zengliang Wang Maimaitili Aisha |
| author_sort | Aierpati Maimaiti |
| collection | DOAJ |
| description | BackgroundThe role of epigenetic modulation in immunity is receiving increased recognition—particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment.MethodsOur study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein–protein interaction network and weighted gene co-expression network analysis.ResultsWe identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered—each with a statistically significant correlation with IA—suggesting their potential as prognostic biological markers.ConclusionOur study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA. |
| first_indexed | 2024-04-13T11:33:00Z |
| format | Article |
| id | doaj.art-5b325d07c1d5492caffd5b2eb73ee70d |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-13T11:33:00Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-5b325d07c1d5492caffd5b2eb73ee70d2022-12-22T02:48:31ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-08-011310.3389/fneur.2022.889141889141m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysmsAierpati Maimaiti0Mirzat Turhon1Mirzat Turhon2Xiaojiang Cheng3Riqing Su4Kaheerman Kadeer5Aximujiang Axier6Dilimulati Ailaiti7Yirizhati Aili8Rena Abudusalamu9Ajimu Kuerban10Zengliang Wang11Maimaitili Aisha12Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurointerventional Surgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurointerventional Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurology, Neurology Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, The First People's Hospital of Kashgar Prefecture, Kashgar, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaBackgroundThe role of epigenetic modulation in immunity is receiving increased recognition—particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment.MethodsOur study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein–protein interaction network and weighted gene co-expression network analysis.ResultsWe identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered—each with a statistically significant correlation with IA—suggesting their potential as prognostic biological markers.ConclusionOur study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA.https://www.frontiersin.org/articles/10.3389/fneur.2022.889141/fullintracranial aneurysmepigeneticsm6A RNA methylationimmune microenvironmentimmunity |
| spellingShingle | Aierpati Maimaiti Mirzat Turhon Mirzat Turhon Xiaojiang Cheng Riqing Su Kaheerman Kadeer Aximujiang Axier Dilimulati Ailaiti Yirizhati Aili Rena Abudusalamu Ajimu Kuerban Zengliang Wang Maimaitili Aisha m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms Frontiers in Neurology intracranial aneurysm epigenetics m6A RNA methylation immune microenvironment immunity |
| title | m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms |
| title_full | m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms |
| title_fullStr | m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms |
| title_full_unstemmed | m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms |
| title_short | m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms |
| title_sort | m6a regulator mediated rna methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms |
| topic | intracranial aneurysm epigenetics m6A RNA methylation immune microenvironment immunity |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.889141/full |
| work_keys_str_mv | AT aierpatimaimaiti m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT mirzatturhon m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT mirzatturhon m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT xiaojiangcheng m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT riqingsu m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT kaheermankadeer m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT aximujiangaxier m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT dilimulatiailaiti m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT yirizhatiaili m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT renaabudusalamu m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT ajimukuerban m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT zengliangwang m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms AT maimaitiliaisha m6aregulatormediatedrnamethylationmodificationpatternsandimmunemicroenvironmentinfiltrationcharacterizationinpatientswithintracranialaneurysms |