Exosomes co-expressing AQP5-targeting miRNAs and IL-4 receptor-binding peptide inhibit the migration of human breast cancer cells.
aquaporin-5
breast cancer
cell migration
exosome
miRNA
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
23
09
2019
revised:
27
12
2019
accepted:
27
12
2019
pubmed:
11
1
2020
medline:
7
10
2020
entrez:
11
1
2020
Statut:
ppublish
Résumé
Aquaporin-5 (AQP5) plays a role in breast cancer cell migration. This study aimed to identify AQP5-targeting miRNAs and examine their effects on breast cancer cell migration through exosome-mediated delivery. Bioinformatic analyses identified miR-1226-3p, miR-19a-3p, and miR-19b-3p as putative regulators of AQP5 mRNA. Immunoblotting revealed a decrease of AQP5 protein abundance when each of these miRNAs was transfected into human breast cancer MDA-MB-231 cells. Quantitative real-time PCR demonstrated the reduction of AQP5 mRNA expression by the transfection of miR-1226-3p and a luciferase reporter assay revealed the reduction of AQP5 translation after the transfection of miR-19b-3p in MDA-MB-231 cells. Consistently, the transfection of each miRNA impeded cell migration. Pathway enrichment analyses showed that these three miRNAs regulate target genes, which were predominantly enriched in the gap junction pathway. For the efficient delivery of AQP5-targeting miRNAs to breast cancer cells, exosomes expressing both miRNAs and a peptide targeting interleukin-4 receptor, which is highly expressed in breast cancer cells, were bioengineered and their inhibitory effects on AQP5 protein expression and cell migration were demonstrated in MDA-MB-231 cells. Taken together, AQP5-regulating miRNAs are identified, which could be exploited for the inhibition of breast cancer cell migration via the exosome-mediated delivery.
Identifiants
pubmed: 31922312
doi: 10.1096/fj.201902434R
doi:
Substances chimiques
AQP5 protein, human
0
Aquaporin 5
0
IL4R protein, human
0
Interleukin-4 Receptor alpha Subunit
0
MicroRNAs
0
Oligopeptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3379-3398Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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