Prior nasal delivery of antagomiR-122 prevents radiation-induced brain injury.
miR-122-5p
microglia
nasal delivery
radiation-induced brain injury
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
24
09
2020
revised:
24
04
2021
accepted:
07
06
2021
pubmed:
27
6
2021
medline:
8
4
2022
entrez:
26
6
2021
Statut:
ppublish
Résumé
Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, influencing the quality of life for the more than 50% of patients who undergo radiation therapy and experience long-term survival. However, no effective treatments are available for these patients, and preventative drugs and effective drug-delivery methods must be developed. Based on our results, miR-122-5p was upregulated in the mouse radiation-induced brain injury (RBI) model and patients with nasopharyngeal carcinoma (NPC) who received radiation therapy. Intranasal administration of a single antagomiR-122-5p dose before irradiation effectively alleviated radiation-induced cognitive impairment, neuronal injury, and neuroinflammation in the mouse RBI model. Results further indicated that miR-122-5p inhibition in microglia reduced the levels of proinflammatory cytokines and enhanced the phagocytic function to protect against radiation-induced neuronal injury in cell models. Further, we profiled transcriptome data and verified that Tensin 1 (TNS1) may be the target of miR-122-5p in RBI. In summary, our results reveal a distinct role for miR-122-5p in regulating neuroinflammation in RBI, indicating that a non-invasive strategy for intranasal miR-122-5p administration may be an attractive therapeutic target in RBI, providing new insights for clinical trials. Further systematic safety assessment, optimization of drug administration, and clarity of mechanism will accelerate the process into clinical practice.
Identifiants
pubmed: 34174438
pii: S1525-0016(21)00325-7
doi: 10.1016/j.ymthe.2021.06.019
pmc: PMC8636282
pii:
doi:
Substances chimiques
Antagomirs
0
MicroRNAs
0
antagomir-122
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3465-3483Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests
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