{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:35Z","timestamp":1785435755641,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2018\/29\/B\/NZ5\/02035"],"award-info":[{"award-number":["2018\/29\/B\/NZ5\/02035"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2018\/29\/B\/NZ5\/02035"],"award-info":[{"award-number":["2018\/29\/B\/NZ5\/02035"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Meningiomas are the most common intracranial tumors. DNA methylation analysis in benign and aggressive meningiomas showed decreased MIR21 methylation and overexpression of hsa-miR-21-5p in atypical and anaplastic tumors. Transcriptomic analysis of distinct WHO grade meningiomas showed multiple predicted hsa-miR-21-5p target genes as differentially expressed. They were mainly related to processes of intercellular and intracellular signaling. Intercellular communication in meningioma was investigated using the deposited scRNA-seq dataset and deconvolution of our RNA-seq data. We found WHO grade-related differences in the microenvironment including inverse correlation between the count of border-associated macrophages (BAM) and the level of hsa-miR-21-5p. Single-cell transcriptomics suggests the role of interleukin 6 in direct communication between tumor cells and BAMs. IL6R and IL6ST are predicted targets of hsa-miR-21-5p downregulated in atypical\/anaplastic meningiomas. IL6R downregulation was also confirmed by immunohistochemistry. Hsa-miR-21-5p enhanced proliferation and viability of KT21-MG1 meningioma cells and showed a regulatory effect on IL6R, IL6ST and other predicted target genes TIMP3, PIK3R, RHOB, and SASH1 by interacting with 3\u2032UTRs. DNA hypomethylation-related overexpression of hsa-miR-21-5p contributes to aggressive meningioma growth by interaction with multiple target genes, and probably affects microenvironment communication between meningioma cells and BAMs by lowering the IL6R level in tumor tissue.<\/jats:p>","DOI":"10.3390\/ijms27104403","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:50:12Z","timestamp":1778835012000},"page":"4403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA Hypomethylation of MIR21 Drives Hsa-miR-21-5p Expression in High-Grade Meningiomas and Reshapes Transcriptomic Signatures of Oncogenic Pathways and Intercellular Communication"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-8137","authenticated-orcid":false,"given":"Paulina","family":"Kober","sequence":"first","affiliation":[{"name":"Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9396-7610","authenticated-orcid":false,"given":"Szymon","family":"Baluszek","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-1763","authenticated-orcid":false,"given":"Beata Joanna","family":"Mossakowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabella","family":"My\u015bliwy","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-134X","authenticated-orcid":false,"given":"Biniyam","family":"Tsegaye","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Ozi\u0119b\u0142o","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3480-0412","authenticated-orcid":false,"given":"Tomasz","family":"Mandat","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-8446","authenticated-orcid":false,"given":"Mateusz","family":"Bujko","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","first-page":"165","article-title":"Primary Brain and Other Central Nervous System Tumors in the United States (2014\u20132018): A Summary of the CBTRUS Statistical Report for Clinicians","volume":"9","author":"Low","year":"2022","journal-title":"Neurooncol. 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