Delivery of miR-424-5p via Extracellular Vesicles Promotes the Apoptosis of MDA-MB-231 TNBC Cells in the Tumor Microenvironment.
Int J Mol Sci
; 22(2)2021 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-33467725
ABSTRACT
Programmed cell death ligand-1 (PD-L1) overexpressed on cancer cells has emerged as a key inhibitor that maintains the immunosuppressive microenvironment through its interaction with the PD-1 receptor in cancer. Here, we demonstrated that miR-424-5p delivery via extracellular vesicles (EVs) derived from adipose tissue-mesenchymal stromal cells (AT-MSCs) partly promotes proinflammation and enhances antitumor cytotoxicity in vitro and in vivo. Triple negative breast cancer (TNBC) exhibits increased expression of PD-L1, and PD-L1 is positively correlated with the overall survival of patients with TNBC. PD-L1 shows relatively higher expression in MDA-MB-231 (MM231) cells and can be downregulated by miR-424-5p. Furthermore, miR-424-5p transported by EVs can increase the secretion of proinflammatory cytokines, decrease the secretion of anti-inflammatory cytokines and promote the apoptosis of tumor cells. The intratumoral administration of miR-424-5p-EVs significantly slowed tumor growth. In conclusion, these results demonstrate that EVs may serve as a delivery system for novel immunotherapies for TNBC through the miR-424-5p/PD-L1 pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
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MicroRNAs
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Microambiente Tumoral
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Células-Tronco Mesenquimais
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Neoplasias de Mama Triplo Negativas
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Vesículas Extracelulares
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article