Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis.
antiangiogenesis
exosome
miRNA
nasopharyngeal carcinoma
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
19 Aug 2020
19 Aug 2020
Historique:
received:
14
04
2020
revised:
01
07
2020
accepted:
14
08
2020
entrez:
14
9
2020
pubmed:
15
9
2020
medline:
15
9
2020
Statut:
aheadofprint
Résumé
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors.
Identifiants
pubmed: 32927364
pii: S2162-2531(20)30246-8
doi: 10.1016/j.omtn.2020.08.017
pmc: PMC7494942
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
153-165Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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