{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:38:46Z","timestamp":1760060326991,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"STI2030-Major Project","award":["#2021ZD0201100","#2021ZD0201105","2022-PUMCH-A-255"],"award-info":[{"award-number":["#2021ZD0201100","#2021ZD0201105","2022-PUMCH-A-255"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["#2021ZD0201100","#2021ZD0201105","2022-PUMCH-A-255"],"award-info":[{"award-number":["#2021ZD0201100","#2021ZD0201105","2022-PUMCH-A-255"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Moyamoya disease (MMD) is a cerebrovascular condition characterized by progressive stenosis of intracranial arteries, leading to stroke. While MMD was long considered a genetic disorder, emerging evidence suggests autoimmune mechanisms may contribute to its pathogenesis. The role of non-coding RNAs (ncRNAs) in the pathogenesis of MMD is under heated discussion, and a competitive endogenous RNA (ceRNA) network involving MMD-related ncRNAs has not been constructed. In this study, we integrated multiple bioinformatic analyses on transcriptomic data from the middle cerebral arteries of MMD patients and controls. Our analysis revealed a significant enrichment of innate immune system pathways, including antigen processing and macrophage activation, in MMD tissue. We constructed a robust ceRNA network centered on the long non-coding RNA MALAT1, identifying 15 core mRNA targets. A classifier built from these MALAT1-related genes accurately distinguished MMD patients from controls, with an area under the curve of 0.869 in independent validation. Furthermore, immune deconvolution analysis showed a marked increase in microvascular endothelial cells and a decrease in CD4+ memory T cells and regulatory T cells in MMD arteries. The expression of the MALAT1 network genes strongly correlated with these shifts in cellular composition, positively with endothelial cells and negatively with T cells. Our findings uncover a MALAT1-driven ceRNA network that links immune dysregulation to vascular changes in MMD, highlighting MALAT1 as a potential biomarker and therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms26167957","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T16:22:33Z","timestamp":1755534153000},"page":"7957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Construction and Analysis of Immune Infiltration and Competing Endogenous RNA Network in Moyamoya Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6610-5532","authenticated-orcid":false,"given":"Wenhao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanhui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9889-9197","authenticated-orcid":false,"given":"Shiyuan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-612X","authenticated-orcid":false,"given":"Jun","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 1, Shuaifuyuan, Dongdan, Dongcheng District, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 1, Shuaifuyuan, Dongdan, Dongcheng District, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1056\/NEJMra0804622","article-title":"Moyamoya disease and moyamoya syndrome","volume":"360","author":"Scott","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/S1474-4422(08)70240-0","article-title":"Moyamoya disease: Current concepts and future perspectives","volume":"7","author":"Kuroda","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1161\/01.STR.14.1.104","article-title":"Moyamoya disease\u2014A review","volume":"14","author":"Suzuki","year":"1983","journal-title":"Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.molmed.2022.08.009","article-title":"Moyamoya disease emerging as an immune-related angiopathy","volume":"28","author":"Asselman","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1161\/STROKEAHA.111.000307","article-title":"Moyamoya disease in a primarily white, midwestern US population: Increased prevalence of autoimmune disease","volume":"44","author":"Bower","year":"2013","journal-title":"Stroke"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jocn.2018.06.055","article-title":"Moyamoya vasculopathy with anti-SCL-70 antibodies: A case report and review of the literature","volume":"56","author":"Ahmad","year":"2018","journal-title":"J. Clin. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1507\/endocrj.EJ22-0319","article-title":"Clinical features of moyamoya disease with Graves\u2019 disease: A retrospective study of 394,422 patients with thyroid disease","volume":"70","author":"Hiruma","year":"2023","journal-title":"Endocr. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"194","DOI":"10.4103\/ajns.AJNS_218_19","article-title":"Coexisting Moyamoya Syndrome and Type 1 Diabetes Mellitus: A Case Report and Review of the Literature","volume":"15","author":"Bolem","year":"2020","journal-title":"Asian J. Neurosurg."},{"key":"ref_9","first-page":"77","article-title":"Moyamoya syndrome associated with Graves\u2019 disease: A case series study","volume":"2","author":"Ni","year":"2014","journal-title":"Ann. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1523\/JNEUROSCI.3389-16.2017","article-title":"Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke","volume":"37","author":"Zhang","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dorschel, K.B., and Wanebo, J.E. (2023). Physiological and pathophysiological mechanisms of the molecular and cellular biology of angiogenesis and inflammation in moyamoya angiopathy and related vascular diseases. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.661611"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.tig.2013.03.002","article-title":"Long noncoding RNAs in development and disease of the central nervous system","volume":"29","author":"Ng","year":"2013","journal-title":"Trends Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature11233","article-title":"Landscape of transcription in human cells","volume":"489","author":"Djebali","year":"2012","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1161\/CIRCRESAHA.114.303265","article-title":"Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth","volume":"114","author":"Michalik","year":"2014","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/ijc.30039","article-title":"From junk to master regulators of invasion: lncRNA functions in migration, EMT and metastasis","volume":"139","author":"Dhamija","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"K\u00f6lling, M., Genschel, C., Kaucsar, T., H\u00fcbner, A., Rong, S., Schmitt, R., S\u00f6rensen-Zender, I., Haddad, G., Kistler, A., and Seeger, H. (2018). Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia\/reperfusion-injury. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-21720-3"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101540","DOI":"10.1016\/j.mcp.2020.101540","article-title":"The knockdown of MALAT1 inhibits the proliferation, invasion and migration of hemangioma endothelial cells by regulating MiR-206\/VEGFA axis","volume":"51","author":"Wang","year":"2020","journal-title":"Mol. Cell. Probes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41401-019-0284-y","article-title":"The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation","volume":"41","author":"Cao","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Santoro, J.D., Lee, S., Wang, A.C., Ho, E., Nagesh, D., Khoshnood, M., Tanna, R., Durazo-Arvizu, R.A., Manning, M.A., and Skotko, B.G. (2021). Increased Autoimmunity in Individuals With Down Syndrome and Moyamoya Disease. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.724969"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jns.2015.02.037","article-title":"Prevalence of autoimmune disease in moyamoya disease patients in Western Chinese population","volume":"351","author":"Chen","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1093\/cvr\/cvy202","article-title":"Immune system-mediated atherosclerosis caused by deficiency of long non-coding RNA MALAT1 in ApoE-\/-mice","volume":"115","author":"Gast","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.jacc.2015.12.051","article-title":"Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets?","volume":"67","author":"Boon","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, Y., Li, S., Zhang, Y., Wang, M., Li, X., Liu, S., Xu, D., Bao, Y., Jia, P., and Wu, N. (2021). The lncRNA Malat1 regulates microvascular function after myocardial infarction in mice via miR-26b-5p\/Mfn1 axis-mediated mitochondrial dynamics. Redox Biol., 41.","DOI":"10.1016\/j.redox.2021.101910"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jaci.2005.02.023","article-title":"Adipose tissue, adipokines, and inflammation","volume":"115","author":"Fantuzzi","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nri2171","article-title":"Evolving functions of endothelial cells in inflammation","volume":"7","author":"Pober","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.smim.2015.10.006","article-title":"Interactions between adipose tissue and the immune system in health and malnutrition","volume":"27","author":"Wensveen","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.smim.2013.10.009","article-title":"The plasticity of human Treg and Th17 cells and its role in autoimmunity","volume":"25","author":"Kleinewietfeld","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_28","first-page":"1","article-title":"LncRNA MALAT1 promotes gastric cancer progression via inhibiting autophagic flux and inducing fibroblast activation","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00011-018-1184-1","article-title":"Long noncoding RNA MALAT1 acts as a competing endogenous RNA to regulate Amadori-glycated albumin-induced MCP-1 expression in retinal microglia by a microRNA-124-dependent mechanism","volume":"67","author":"Dong","year":"2018","journal-title":"Inflamm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11010-020-03684-z","article-title":"MALAT1 affects hypoxia-induced vascular endothelial cell injury and autophagy by regulating miR-19b-3p\/HIF-1alpha axis","volume":"466","author":"Liu","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhao, R., Zhu, Y., Yang, X., Duan, T., Yang, J., Chen, B., Yang, X., Ni, G., Li, S., and He, Y. (2025). Inorganic Arsenic-Induced Up-Regulation of MALAT1 Affects Cell Apoptosis via Disrupting the Binding Between IKBalpha and IKKbeta, P65. J. Biochem. Mol. Toxicol., 39.","DOI":"10.1002\/jbt.70374"},{"key":"ref_32","first-page":"302","article-title":"IL-6 induced lncRNA MALAT1 enhances TNF-alpha expression in LPS-induced septic cardiomyocytes via activation of SAA3","volume":"21","author":"Zhuang","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1080\/0886022X.2018.1487863","article-title":"The long non-coding RNA MALAT1 is increased in renal ischemia-reperfusion injury and inhibits hypoxia-induced inflammation","volume":"40","author":"Tian","year":"2018","journal-title":"Ren. Fail."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1161\/01.CIR.102.14.1697","article-title":"Direct evidence for cytokine involvement in neointimal hyperplasia","volume":"102","author":"Rectenwald","year":"2000","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3171\/2010.5.PEDS09505","article-title":"Diffuse and uncontrolled vascular smooth muscle cell proliferation in rapidly progressing pediatric moyamoya disease","volume":"6","author":"Reid","year":"2010","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/WNR.0000000000002157","article-title":"Long noncoding RNA MALAT1 promotes angiogenesis through the caveolin-1\/VEGF pathway after cerebral ischemic injury","volume":"36","author":"Lin","year":"2025","journal-title":"Neuroreport"},{"key":"ref_37","first-page":"e10994","article-title":"Moyamoya: An Update and Review","volume":"12","author":"Berry","year":"2020","journal-title":"Cureus"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Fang, Y.C., Wei, L.F., Hu, C.J., and Tu, Y.K. (2021). Pathological Circulating Factors in Moyamoya Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041696"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E3","DOI":"10.3171\/2021.6.FOCUS20870","article-title":"Transcriptome-wide analysis of intracranial artery in patients with moyamoya disease showing upregulation of immune response, and downregulation of oxidative phosphorylation and DNA repair","volume":"51","author":"Kanamori","year":"2021","journal-title":"Neurosurg. Focus."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The sva package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Arikawa, E., Sun, Y., Wang, J., Zhou, Q., Ning, B., Dial, S.L., Guo, L., and Yang, J. (2008). Cross-platform comparison of SYBR Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-328"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Romero, P. (2011). Pre-processing and differential expression analysis of Agilent microRNA arrays using the AgiMicroRna Bioconductor library. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-64"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zahurak, M., Parmigiani, G., Yu, W., Scharpf, R.B., Berman, D., Schaeffer, E., Shabbeer, S., and Cope, L. (2007). Pre-processing Agilent microarray data. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-142"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gku631","article-title":"The multiMiR R package and database: Integration of microRNA-target interactions along with their disease and drug associations","volume":"42","author":"Ru","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1093\/nar\/gkw116","article-title":"Distribution of miRNA expression across human tissues","volume":"44","author":"Ludwig","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D92","DOI":"10.1093\/nar\/gkt1248","article-title":"starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data","volume":"42","author":"Li","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-1-0716-0327-7_16","article-title":"Immunedeconv: An R Package for Unified Access to Computational Methods for Estimating Immune Cell Fractions from Bulk RNA-Sequencing Data","volume":"2120","author":"Sturm","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, F., Coates, B., Zhang, Y., Zhou, X., and Cheng, D. (2016). Comparative profiling of microRNAs in the winged and wingless English grain aphid, Sitobion avenae (F.) (Homoptera: Aphididae). Sci. Rep., 6.","DOI":"10.1038\/srep35668"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7957\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:29:53Z","timestamp":1760034593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":51,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26167957"],"URL":"https:\/\/doi.org\/10.3390\/ijms26167957","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,8,18]]}}}