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Due to the concurrent deregulation of numerous genes in glioblastoma, molecular monotherapies have not improved clinical outcomes. Evidence suggests that targeting multiple deregulated molecules is essential for better therapies; however, this is limited by the lack of suitable drugs and increased toxicity of combination therapies. To address this, we hypothesized that miRNAs, small gene-regulatory RNAs that suppress mRNA, could simultaneously inhibit multiple deregulated genes in glioblastoma and be used for more effective therapies. We identified regulatory miRNAs \u2014 those that target several deregulated genes in glioblastoma \u2014 using a combination of PAR-CLIP screening, TCGA data analyses, and an algorithm to rank target importance and miRNA therapeutic potential. We selected 2 tumor-suppressive miRNAs, miR-340 and miR-382, and 1 oncogenic miRNA, miR-17, and showed that they targeted critical glioblastoma pathways and altered cell growth, survival, invasion, and in vivo tumor growth. We developed and successfully applied a miRNA therapeutic delivery approach using brain-penetrating nanoparticles combined with MRI-guided focused ultrasound and microbubbles, to inhibit established tumor growth and extend animal survival. This strategy offers a promising approach for translating miRNA-based therapies into clinical trials for glioblastoma and other cancers.<\/jats:p>\n                  <jats:p>We developed and used new computational, experimental, and therapeutic approaches to identify and therapeutically deliver master regulatory miRNAs to inhibit the growth of glioblastoma, the most common and deadly primary brain tumor.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1172\/jci195639","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:52:22Z","timestamp":1782841942000},"source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic delivery of microRNAs discovered to target deregulated glioblastoma pathways inhibits tumor growth in mice"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-3000","authenticated-orcid":true,"given":"Shekhar","family":"Saha","sequence":"first","affiliation":[{"name":"Department of 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