The Construction and Analysis of Immune Infiltration and Competing Endogenous RNA Network in Acute Ischemic Stroke

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2022 Jun 3

PMID 35656537

Authors

Zhaolei Ma

Chun-Feng Liu

Li Zhang

Ning Xiang

Yifan Zhang

Lan Chu

Affiliations

Soon will be listed here.

Abstract

Acute ischemic stroke (AIS) is a common neurological disease that seriously endangers both the physical and mental health of human. After AIS, activated immune cells are recruited to the stroke site, where inflammatory mediators are released locally, and severe immune inflammatory reactions occur within a short time, which affects the progress and prognosis of IS. Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a closed-loop structure and high stability. Studies have found that circRNA can affect the course of IS. However, there is no report on ceRNA's pathogenesis in AIS that is mediated by circRNA. In this study, the CIBERSORT algorithm was used to analyze the distribution of immune cells in patients with AIS. mRNA dataset was downloaded from the GEO database, and the weighted gene co-expression network analysis (WGCNA) method was used to construct weighted gene co-expression to determine 668 target genes, using GO, KEGG enrichment analysis, construction of protein-protein interaction (PPI) network analysis, and molecular complex detection (MCODE) plug-in analysis. The results showed that the biological function of the target gene was in line with the activation and immune regulation of neutrophils; signal pathways were mostly enriched in immune inflammation-related pathways. A Venn diagram was used to obtain 52 intersection genes between target genes and disease genes. By analyzing the correlation between the intersection genes and immune cells, we found that the top 5 hub genes were TOM1, STAT3, RAB3D, MDM2, and FOS, which were all significantly positively correlated with neutrophils and significantly negatively correlated with eosinophils. A total of 52 intersection genes and the related circRNA and miRNA were used as input for Cytoscape software to construct a circRNA-mediated ceRNA competition endogenous network, where a total of 18 circRNAs were found. Further analysis of the correlation between circRNA and immune cells found that 4 circRNAs are positively correlated with neutrophils. Therefore, we speculate that there may be a regulatory relationship between circRNA-mediated ceRNA and the immune mechanism in AIS. This study has important guiding significance for the progress, outcome of AIS, and the development of new medicine.

Citing Articles

Epigenetic regulation of the inflammatory response in stroke.

Liang J, Yang F, Li Z, Li Q Neural Regen Res. 2024; 20(11):3045-3062.

PMID: 39589183 PMC: 11881735. DOI: 10.4103/NRR.NRR-D-24-00672.

Identification of core genes shared by ischemic stroke and myocardial infarction using an integrated approach.

Wang M, Gao Y, Chen H, Cheng J, Wang G Medicine (Baltimore). 2024; 103(27):e38877.

PMID: 38968466 PMC: 11224832. DOI: 10.1097/MD.0000000000038877.

Integrating Bulk RNA and Single-Cell Sequencing Data Unveils Efferocytosis Patterns and ceRNA Network in Ischemic Stroke.

Yuan J, Liao Y, Zhang T, Tang Y, Yu P, Liu Y Transl Stroke Res. 2024; .

PMID: 38678526 DOI: 10.1007/s12975-024-01255-8.

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

Geng Y, Liu Y, Wang M, Dong X, Sun X, Luo Y Front Immunol. 2024; 14:1320475.

PMID: 38268925 PMC: 10806171. DOI: 10.3389/fimmu.2023.1320475.

Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke.

Lu D, Cai H, Li Y, Chang W, Liu X, Dai Q Aging (Albany NY). 2023; 15(24):14803-14829.

PMID: 38112574 PMC: 10781493. DOI: 10.18632/aging.205308.

References

Gruenbaum Y, Margalit A, Goldman R, Shumaker D, Wilson K . The nuclear lamina comes of age. Nat Rev Mol Cell Biol. 2005; 6(1):21-31. DOI: 10.1038/nrm1550. View

Kang L, Yu H, Yang X, Zhu Y, Bai X, Wang R . Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke. Nat Commun. 2020; 11(1):2488. PMC: 7237502. DOI: 10.1038/s41467-020-16191-y. View

Gan L, Liao S, Xing Y, Deng S . The Regulatory Functions of lncRNAs on Angiogenesis Following Ischemic Stroke. Front Mol Neurosci. 2021; 13:613976. PMC: 7890233. DOI: 10.3389/fnmol.2020.613976. View

Stamova B, Jickling G, Ander B, Zhan X, Liu D, Turner R . Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic. PLoS One. 2014; 9(7):e102550. PMC: 4103830. DOI: 10.1371/journal.pone.0102550. View

Vajen T, Koenen R, Werner I, Staudt M, Projahn D, Curaj A . Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis. Sci Rep. 2018; 8(1):10647. PMC: 6045661. DOI: 10.1038/s41598-018-29026-0. View

Tarkanyi G, Karadi Z, Szabo Z, Szegedi I, Csiba L, Szapary L . Relationship between leukocyte counts and large vessel occlusion in acute ischemic stroke. BMC Neurol. 2020; 20(1):440. PMC: 7716438. DOI: 10.1186/s12883-020-02017-3. View

Yang L, Han B, Zhang Z, Wang S, Bai Y, Zhang Y . Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models. Circulation. 2020; 142(6):556-574. DOI: 10.1161/CIRCULATIONAHA.120.045765. View

Emsley H, Smith C, Gavin C, Georgiou R, Vail A, Barberan E . An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol. 2003; 139(1-2):93-101. DOI: 10.1016/s0165-5728(03)00134-6. View

Fu Y, Liu Q, Anrather J, Shi F . Immune interventions in stroke. Nat Rev Neurol. 2015; 11(9):524-35. PMC: 4851339. DOI: 10.1038/nrneurol.2015.144. View

10.

Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N . Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 2013; 1833(12):3448-3459. DOI: 10.1016/j.bbamcr.2013.06.001. View

11.

Cho M, Cho K, Kang H, Jeon E, Kim H, Kwon H . Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy. 2014; 10(10):1761-75. PMC: 4198361. DOI: 10.4161/auto.29647. View

12.

Li Y, Wang Y, Yao Y, Griffiths B, Feng L, Tao T . Systematic Study of the Immune Components after Ischemic Stroke Using CyTOF Techniques. J Immunol Res. 2020; 2020:9132410. PMC: 7474762. DOI: 10.1155/2020/9132410. View

13.

Rajkovic O, Potjewyd G, Pinteaux E . Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke. Front Neurol. 2018; 9:734. PMC: 6129611. DOI: 10.3389/fneur.2018.00734. View

14.

Hong Y, Liu Y, Zhang G, Wu H, Hou Y . Progesterone suppresses Aβ-induced neuroinflammation by enhancing autophagy in astrocytes. Int Immunopharmacol. 2017; 54:336-343. DOI: 10.1016/j.intimp.2017.11.044. View

15.

Zhao H, Qin W, Wang P, Wen Z . Eosinopenia is a predictive factor for the severity of acute ischemic stroke. Neural Regen Res. 2019; 14(10):1772-1779. PMC: 6585555. DOI: 10.4103/1673-5374.258411. View

16.

Li S, Cao Y, Zhang H, Lu X, Wang T, Xu S . Construction of lncRNA-Mediated ceRNA Network for Investigating Immune Pathogenesis of Ischemic Stroke. Mol Neurobiol. 2021; 58(9):4758-4769. DOI: 10.1007/s12035-021-02426-6. View

17.

Ding M, Lozoya E, Rico R, Chew S . The Role of Angiogenesis-Inducing microRNAs in Vascular Tissue Engineering. Tissue Eng Part A. 2020; 26(23-24):1283-1302. DOI: 10.1089/ten.TEA.2020.0170. View

18.

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B . STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 2003; 31(1):258-61. PMC: 165481. DOI: 10.1093/nar/gkg034. View

19.

Harris M, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R . The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 2003; 32(Database issue):D258-61. PMC: 308770. DOI: 10.1093/nar/gkh036. View

20.

Yang Z, Zhong L, Zhong S, Xian R, Yuan B . Hypoxia induces microglia autophagy and neural inflammation injury in focal cerebral ischemia model. Exp Mol Pathol. 2015; 98(2):219-24. DOI: 10.1016/j.yexmp.2015.02.003. View