Heterogeneous Nuclear Ribonucleoprotein A1 Loads Batched Tumor-Promoting MicroRNAs Into Small Extracellular Vesicles With the Assist of Caveolin-1 in A549 Cells.
RNA binding protein
SUMOylation
extracellular vesicles
miRNA—microRNA
sorting mechanism
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
03
2021
accepted:
11
05
2021
entrez:
5
7
2021
pubmed:
6
7
2021
medline:
6
7
2021
Statut:
epublish
Résumé
MicroRNAs in small extracellular vesicle (sEV-miRNAs) have been widely investigated as crucial regulated molecules secreted by tumor cells to communicate with surroundings. It is of great significance to explore the loading mechanism of sEV-miRNAs by tumor cells. Here, we comprehensively illustrated a reasoned loading pathway of batched tumor-promoting sEV-miRNAs in non-small cell lung cancer (NSCLC) cell line A549 with the application of a multi-omics method. The protein heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was strictly selected as a powerful sEV-miRNA loading protein from miRNA-binding proteome and further verified through small RNA sequencing after hnRNPA1 silence. In terms of the mechanism, SUMOylated hnRNPA1 in sEVs was verified to control sEV-miRNA loading. Subsequently, as a scaffolding component of caveolae, caveolin-1 (CAV1) was detailedly demonstrated to assist the loading of SUMOylated hnRNPA1 and its binding miRNAs into sEVs. Inhibition of CAV1 significantly prevented SUMOylated hnRNPA1 from encapsulating into sEVs, resulting in less enrichment of sEV-miRNAs it loaded. Finally, we confirmed that hnRNPA1-loaded sEV-miRNAs could facilitate tumor proliferation and migration based on database analysis and cytological experiments. Our findings reveal a loading mechanism of batched tumor-promoting sEV-miRNAs, which may contribute to the selection of therapeutic targets for lung cancer.
Identifiants
pubmed: 34222256
doi: 10.3389/fcell.2021.687912
pmc: PMC8245771
doi:
Types de publication
Journal Article
Langues
eng
Pagination
687912Informations de copyright
Copyright © 2021 Li, Zhang, Li, Guo, Li, Zhang, Li and Mi.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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