OSCR

Therapeutic delivery of microRNAs discovered to target deregulated glioblastoma pathways inhibits tumor growth in mice.

Overview

Authors: Shekhar Saha1, Ying Zhang1, Myron K. Gibert Jr.1, Collin Dube1, Farina Hanif1,2, Elizabeth Qian Xu Mulcahy1, Sylwia Bednarek1, Yunan Sun1, Pawel Marcinkiewicz1, Xiantao Wang3, Gijung Kwak4,5, Ahsan Polash3, Haolin Li4,5,6, Kadie Hudson1, Manikarna Dinda7, Tapas Saha8, Matthew McCord9, Fadila Guessous1,10, Nichola Cruickshanks1, Rossymar Rivera Colon1
and 13 other authorsLily Dell’Olio1, Rajitha Anbu1, Wenjie Liu1, Songy Choi1, Benjamin Kefas1,11, Pankaj Kumar12, Alexander L. Klibanov13, David Schiff14, Jung Soo Suk4,5,6,15, Justin Hanes16, Jamie Mata17, Markus Hafner3, Roger Abounader1,14,18,19
ORCID iDs: Shekhar Saha, Haolin Li
19 affiliations
  1. Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  2. Department of Biochemistry, Dow International Medical College, Dow University of Health Sciences, OJHA Campus, Karachi, Pakistan
  3. National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA
  4. Department of Neurosurgery and
  5. Medicine Institute for Neuroscience Discovery (UM-MIND), School of Medicine, University of Maryland, Baltimore, Maryland, USA
  6. Department of Chemical and Biomolecular Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA
  7. Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  8. Swiss Re, Healthcare, Bengaluru, India
  9. Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  10. Laboratory of Onco-Pathology, Biology and Cancer Environment, Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca, Morocco
  11. Pharmacy, University of Virginia, Charlottesville, Virginia, USA
  12. Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  13. Division of Cardiovascular Medicine and
  14. Department of Neurology, University of Virginia, Charlottesville, Virginia, USA
  15. Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  16. Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  17. Department of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  18. Comprehensive Cancer Center and
  19. Center for RNA Science and Medicine, University of Virginia, Charlottesville, Virginia, USA
Institutions: University of Virginia (United States); Dow University of Health Sciences (Pakistan); National Institutes of Health (United States); National Institute of Arthritis and Musculoskeletal and Skin Diseases (United States); University of Maryland, Baltimore (United States); Johns Hopkins University (United States); Université Mohammed VI des Sciences et de la Santé (Morocco); Johns Hopkins Medicine (United States)
Journal: The Journal of clinical investigation, volume 136, issue 16, article e195639
Dates: received 20 May 2025; accepted 24 June 2026; published online 30 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1172/jci195639 · PMID 42378058 · PMCID PMC13476142 · OpenAlex W7166734572
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: fMRI & imaging, Statistics
Keywords: Cell biology, Oncology, Brain cancer, Noncoding RNAs
MeSH: Brain Neoplasms*, Glioblastoma*, MicroRNAs*, RNA, Neoplasm*, Animals, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Mice, Xenograft Model Antitumor Assays (* major topic)
Topic: MicroRNA in disease regulation (Cancer Research, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Cancer Institute (UO1 CA220841, P30CA044579); HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (RO1 NS122222, 1R21NS122136)
Citations: cited by 1 paper (Europe PMC); 53 references in the paper

Abstract

Glioblastoma is a fatal primary malignant brain tumor, with an average survival of 15 months despite surgical resection, chemotherapy, and radiation therapy. 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 — those that target several deregulated genes in glioblastoma — 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

Datasets cited

Data availability

The PAR-CLIP dataset generated in this study has been deposited in the Gene Expression Omnibus under accession number GSE293517. All the data values are reported in the Supporting Data Values file (https://github.com/ss7st/miRNA_PARCLIP_analysis.git). All codes and materials supporting the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 33 authors, 4 keywords, 10 MeSH terms, 2 funders, 53 references.

Cite

This paper

Saha, S., Zhang, Y., Gibert, M. K., Dube, C., Hanif, F., Mulcahy, E. Q. X., Bednarek, S., Sun, Y., Marcinkiewicz, P., Wang, X., Kwak, G., Polash, A., Li, H., Hudson, K., Dinda, M., Saha, T., McCord, M., Guessous, F., Cruickshanks, N., . . . Abounader, R. (2026). Therapeutic delivery of microRNAs discovered to target deregulated glioblastoma pathways inhibits tumor growth in mice. The Journal of clinical investigation, 136(16), e195639. https://doi.org/10.1172/jci195639

BibTeX

@article{saha2026therapeutic,
author = {Saha, Shekhar and Zhang, Ying and Gibert, Myron K. and Dube, Collin and Hanif, Farina and Mulcahy, Elizabeth Qian Xu and Bednarek, Sylwia and Sun, Yunan and Marcinkiewicz, Pawel and Wang, Xiantao and Kwak, Gijung and Polash, Ahsan and Li, Haolin and Hudson, Kadie and Dinda, Manikarna and Saha, Tapas and McCord, Matthew and Guessous, Fadila and Cruickshanks, Nichola and Rivera Colon, Rossymar and Dell’Olio, Lily and Anbu, Rajitha and Liu, Wenjie and Choi, Songy and Kefas, Benjamin and Kumar, Pankaj and Klibanov, Alexander L. and Schiff, David and Suk, Jung Soo and Hanes, Justin and Mata, Jamie and Hafner, Markus and Abounader, Roger},
title = {{Therapeutic delivery of microRNAs discovered to target deregulated glioblastoma pathways inhibits tumor growth in mice}},
journal = {The Journal of clinical investigation},
year = {2026},
month = jun,
volume = {136},
number = {16},
pages = {e195639},
publisher = {American Society for Clinical Investigation},
issn = {0021-9738},
doi = {10.1172/jci195639},
url = {https://doi.org/10.1172/jci195639},
pmid = {42378058},
pmcid = {PMC13476142}
}

RIS

TY - JOUR
AU - Saha, Shekhar
AU - Zhang, Ying
AU - Gibert, Myron K.
AU - Dube, Collin
AU - Hanif, Farina
AU - Mulcahy, Elizabeth Qian Xu
AU - Bednarek, Sylwia
AU - Sun, Yunan
AU - Marcinkiewicz, Pawel
AU - Wang, Xiantao
AU - Kwak, Gijung
AU - Polash, Ahsan
AU - Li, Haolin
AU - Hudson, Kadie
AU - Dinda, Manikarna
AU - Saha, Tapas
AU - McCord, Matthew
AU - Guessous, Fadila
AU - Cruickshanks, Nichola
AU - Rivera Colon, Rossymar
AU - Dell’Olio, Lily
AU - Anbu, Rajitha
AU - Liu, Wenjie
AU - Choi, Songy
AU - Kefas, Benjamin
AU - Kumar, Pankaj
AU - Klibanov, Alexander L.
AU - Schiff, David
AU - Suk, Jung Soo
AU - Hanes, Justin
AU - Mata, Jamie
AU - Hafner, Markus
AU - Abounader, Roger
TI - Therapeutic delivery of microRNAs discovered to target deregulated glioblastoma pathways inhibits tumor growth in mice
T2 - The Journal of clinical investigation
J2 - J Clin Invest
PY - 2026
DA - 2026/06/30
VL - 136
IS - 16
SP - e195639
SN - 0021-9738
PB - American Society for Clinical Investigation
DO - 10.1172/jci195639
UR - https://doi.org/10.1172/jci195639
LA - en
ER -

CSL-JSON

{
"id": "10.1172/jci195639",
"type": "article-journal",
"title": "Therapeutic delivery of microRNAs discovered to target deregulated glioblastoma pathways inhibits tumor growth in mice",
"container-title": "The Journal of clinical investigation",
"author": [
{
"family": "Saha",
"given": "Shekhar"
},
{
"family": "Zhang",
"given": "Ying"
},
{
"family": "Gibert",
"given": "Myron K."
},
{
"family": "Dube",
"given": "Collin"
},
{
"family": "Hanif",
"given": "Farina"
},
{
"family": "Mulcahy",
"given": "Elizabeth Qian Xu"
},
{
"family": "Bednarek",
"given": "Sylwia"
},
{
"family": "Sun",
"given": "Yunan"
},
{
"family": "Marcinkiewicz",
"given": "Pawel"
},
{
"family": "Wang",
"given": "Xiantao"
},
{
"family": "Kwak",
"given": "Gijung"
},
{
"family": "Polash",
"given": "Ahsan"
},
{
"family": "Li",
"given": "Haolin"
},
{
"family": "Hudson",
"given": "Kadie"
},
{
"family": "Dinda",
"given": "Manikarna"
},
{
"family": "Saha",
"given": "Tapas"
},
{
"family": "McCord",
"given": "Matthew"
},
{
"family": "Guessous",
"given": "Fadila"
},
{
"family": "Cruickshanks",
"given": "Nichola"
},
{
"family": "Rivera Colon",
"given": "Rossymar"
},
{
"family": "Dell’Olio",
"given": "Lily"
},
{
"family": "Anbu",
"given": "Rajitha"
},
{
"family": "Liu",
"given": "Wenjie"
},
{
"family": "Choi",
"given": "Songy"
},
{
"family": "Kefas",
"given": "Benjamin"
},
{
"family": "Kumar",
"given": "Pankaj"
},
{
"family": "Klibanov",
"given": "Alexander L."
},
{
"family": "Schiff",
"given": "David"
},
{
"family": "Suk",
"given": "Jung Soo"
},
{
"family": "Hanes",
"given": "Justin"
},
{
"family": "Mata",
"given": "Jamie"
},
{
"family": "Hafner",
"given": "Markus"
},
{
"family": "Abounader",
"given": "Roger"
}
],
"container-title-short": "J Clin Invest",
"volume": "136",
"issue": "16",
"page": "e195639",
"DOI": "10.1172/jci195639",
"PMID": "42378058",
"PMCID": "PMC13476142",
"ISSN": "0021-9738",
"publisher": "American Society for Clinical Investigation",
"URL": "https://doi.org/10.1172/jci195639",
"language": "en",
"issued": {
"date-parts": [
[
2026,
6,
30
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1158/2767-9764.crc-25-0579 [code]
Glioblastoma Subtypes Exhibit Distinct Migration Mechanics and Immune Responses.
Journal: Cancer research communications
In common: other condition, mouse, 3 references
[2] doi:10.1007/s11060-026-05635-y
From relapse to survival: real-world clinical impact of a multimodal approach in first-time recurrent glioblastoma : FROST: multimodal treatment for GBM recurrence.
Journal: Journal of neuro-oncology
In common: other condition, 3 references
[3] doi:10.1002/glia.70142
The Ubiquitin Ligase Zinc Finger SWIM Domain-Containing Protein 8 Regulates Oligodendrocyte Development Through the Argonaute2/MicroRNA-7 Axis.
Journal: Glia
In common: mouse, cellular / molecular, 2 references
[4] doi:10.3390/ijms27167240
1-Piperidine Propionic Acid Inhibits PAR2/SerpinB3 Signaling and Reduces Glioblastoma Tumor Aggressiveness.
Journal: International journal of molecular sciences
In common: other condition, mouse, cellular / molecular, 2 references
[5] doi:10.1016/j.omton.2026.201201
Enable CAR T cell immunotherapy in glioblastoma by modifying its microenvironment via oncolytic adenovirus encoding bispecific T cell engager.
Journal: Molecular therapy. Oncology
In common: other condition, cellular / molecular, 2 references
[6] doi:10.1080/17501911.2026.2691031
Promoter methylation-associated brain-enriched long noncoding RNAs in glioblastoma: a multi-cohort public epigenomic re-analysis.
Journal: Epigenomics
In common: other condition, cellular / molecular, 2 references
[7] doi:10.1016/j.celrep.2026.117314
GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.
Journal: Cell reports
In common: other condition, mouse, cellular / molecular, 1 reference
[8] doi:10.1371/journal.pone.0351405 [code]
Unimodal vs. multimodal deep learning for non-invasive MGMT promoter methylation prediction in glioblastoma: A systematic evaluation on the BraTS 2021 dataset.
Journal: PloS one
In common: other condition, 2 references
[9] doi:10.3390/ijms27177542
Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model.
Journal: International journal of molecular sciences
In common: other condition, mouse, cellular / molecular, 1 reference
[10] doi:10.3389/fphar.2026.1797067
Network-driven prioritization and functional phenotyping nominate TTC23 as a biomarker-informed target in chlorpromazine repurposing for glioblastoma.
Journal: Frontiers in pharmacology
In common: other condition, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.