PMID- 35989938 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220823 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 13 DP - 2022 TI - m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms. PG - 889141 LID - 10.3389/fneur.2022.889141 [doi] LID - 889141 AB - BACKGROUND: The 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. METHODS: Our 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. RESULTS: We 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. CONCLUSION: Our 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. CI - Copyright (c) 2022 Maimaiti, Turhon, Cheng, Su, Kadeer, Axier, Ailaiti, Aili, Abudusalamu, Kuerban, Wang and Aisha. FAU - Maimaiti, Aierpati AU - Maimaiti A AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Turhon, Mirzat AU - Turhon M AD - Department of Neurointerventional Surgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. AD - Department of Neurointerventional Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. FAU - Cheng, Xiaojiang AU - Cheng X AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Su, Riqing AU - Su R AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Kadeer, Kaheerman AU - Kadeer K AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Axier, Aximujiang AU - Axier A AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Ailaiti, Dilimulati AU - Ailaiti D AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Aili, Yirizhati AU - Aili Y AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Abudusalamu, Rena AU - Abudusalamu R AD - Department of Neurology, Neurology Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Kuerban, Ajimu AU - Kuerban A AD - Department of Neurosurgery, The First People's Hospital of Kashgar Prefecture, Kashgar, China. FAU - Wang, Zengliang AU - Wang Z AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Aisha, Maimaitili AU - Aisha M AD - Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. LA - eng PT - Journal Article DEP - 20220805 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC9389407 OTO - NOTNLM OT - epigenetics OT - immune microenvironment OT - immunity OT - intracranial aneurysm OT - m6A RNA methylation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/23 06:00 MHDA- 2022/08/23 06:01 PMCR- 2022/08/05 CRDT- 2022/08/22 03:47 PHST- 2022/03/08 00:00 [received] PHST- 2022/06/23 00:00 [accepted] PHST- 2022/08/22 03:47 [entrez] PHST- 2022/08/23 06:00 [pubmed] PHST- 2022/08/23 06:01 [medline] PHST- 2022/08/05 00:00 [pmc-release] AID - 10.3389/fneur.2022.889141 [doi] PST - epublish SO - Front Neurol. 2022 Aug 5;13:889141. doi: 10.3389/fneur.2022.889141. eCollection 2022.