{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:15:28Z","timestamp":1783707328115,"version":"3.55.0"},"reference-count":13,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Glioblastoma multiforme (GBM) is the most aggressive and lethal primary tumor of the central nervous system. MicroRNAs (miRNAs) are key post transcriptional regulators of gene expression, and increasing evidence suggests that miRNA relationships may contribute to regulatory complexity in cancer biology. In this study, we combined\n                    <jats:italic>in silico<\/jats:italic>\n                    analyses of ten independent miRNA expression datasets (TCGA and GEO) with functional validation in GBM cell models to investigate the association between miR-132 and miR-21 in GBM. Differential expression analysis consistently demonstrated significant overexpression of miR-21-5p and downregulation of miR-132-3p in GBM tissues compared with normal brain. These findings were validated in U87 and C6 GBM cell lines using qRT-PCR, confirming consistent dysregulation of both miRNAs in vitro (p\u2009&lt;\u20090.05). Functional experiments demonstrated that miR-132 overexpression is associated with reduced miR-21 expression and increased expression of established miR-21 target genes, including\n                    <jats:italic>BMPR2<\/jats:italic>\n                    and\n                    <jats:italic>BCL11B<\/jats:italic>\n                    at both mRNA and protein levels. These molecular changes were accompanied by reduced metabolic activity, impaired wound closure, and increased apoptotic cell death in both U87 and C6 GBM models. Collectively, these findings support a strong functional association between miR-132 expression and miR-21 related regulatory networks and phenotypic changes in GBM. However, the present study does not provide evidence for a direct physical or fundamental interaction between miR-132 and miR-21. Further mechanistic studies, including rescue experiments and direct binding assays, are required to clarify the underlying regulatory mechanisms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352119","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:37:21Z","timestamp":1783705041000},"page":"e0352119","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-132 overexpression is associated with modulation in miR-21 expression and glioblastoma cell behavior"],"prefix":"10.1371","volume":"21","author":[{"given":"Kimia","family":"Abdi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Bayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3300-6332","authenticated-orcid":true,"given":"Seyed Javad","family":"Mowla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"pone.0352119.ref001","article-title":"An atlas of causal and mechanistic drivers of interpatient heterogeneity in glioma","author":"S Turkarslan","year":"2024","journal-title":"medRxiv"},{"issue":"3","key":"pone.0352119.ref002","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3390\/cancers16030589","article-title":"Multiparametric Radiogenomic Model to Predict Survival in Patients with Glioblastoma","volume":"16","author":"K Mahmoudi","year":"2024","journal-title":"Cancers (Basel)"},{"key":"pone.0352119.ref003","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.omtn.2023.04.001","article-title":"Synthetic miR-21 decoy circularized by tRNA splicing mechanism inhibited tumorigenesis in glioblastoma in vitro and in vivo models.","volume":"32","author":"H Bayat","year":"2023","journal-title":"Mol Ther Nucleic Acids."},{"issue":"11","key":"pone.0352119.ref004","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.3390\/brainsci13111602","article-title":"Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings","volume":"13","author":"E Begagi\u0107","year":"2023","journal-title":"Brain Sci"},{"key":"pone.0352119.ref005","doi-asserted-by":"crossref","first-page":"175956","DOI":"10.1016\/j.ejphar.2023.175956","article-title":"Development of microRNA-based therapeutics for central nervous system diseases","volume":"956","author":"S Xia","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"pone.0352119.ref006","doi-asserted-by":"crossref","first-page":"782","DOI":"10.3389\/fonc.2019.00782","article-title":"Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma","volume":"9","author":"H Monfared","year":"2019","journal-title":"Front Oncol"},{"issue":"4","key":"pone.0352119.ref007","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.047662","article-title":"miRNA interplay: mechanisms and consequences in cancer","volume":"14","author":"M Hill","year":"2021","journal-title":"Dis Model Mech"},{"issue":"1","key":"pone.0352119.ref008","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.tcb.2020.10.005","article-title":"Global miRNA to miRNA interactions: impacts for miR-21","volume":"31","author":"M Hill","year":"2021","journal-title":"Trends Cell Biol"},{"issue":"2","key":"pone.0352119.ref009","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3892\/ol.2020.12380","article-title":"miR-21-5p promotes cell proliferation by targeting BCL11B in Thp-1 cells","volume":"21","author":"L Zhang","year":"2021","journal-title":"Oncol Lett"},{"issue":"6","key":"pone.0352119.ref010","doi-asserted-by":"crossref","DOI":"10.1152\/ajplung.00316.2011","article-title":"miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling","volume":"302","author":"S Yang","year":"2012","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"1","key":"pone.0352119.ref011","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/21655979.2019.1710925","article-title":"MiR-132 inhibits migration and invasion and increases chemosensitivity of cisplatin-resistant oral squamous cell carcinoma cells via targeting TGF-\u03b21","volume":"11","author":"L Chen","year":"2020","journal-title":"Bioengineered"},{"issue":"6","key":"pone.0352119.ref012","doi-asserted-by":"crossref","first-page":"106829","DOI":"10.1016\/j.isci.2023.106829","article-title":"microRNA-132 regulates gene expression programs involved in microglial homeostasis","volume":"26","author":"H Walgrave","year":"2023","journal-title":"iScience"},{"issue":"4","key":"pone.0352119.ref013","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1093\/nar\/gkx1254","article-title":"Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level","volume":"46","author":"D Wang","year":"2018","journal-title":"Nucleic Acids Res"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0352119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:37:24Z","timestamp":1783705044000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0352119"}},"subtitle":[],"editor":[{"given":"Suzie","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":13,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0352119","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]}}}