Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action.
Journal
EMBO reports
Series/Report No.
EMBO Reports
Journal Volume
25
Journal Issue
5
Start Page
2441
End Page
2478
ISSN
1469-3178
Date Issued
2024-05
Author(s)
Lin, Meng-Chieh
Chen, Shih-Yin
Hsu, Jing-Ya
Lu, Li-Yu
Wang, Chen-Chi
Chen, Yi-Ju
Tsai, Jia-Shiuan
Li, Hua-Jung
DOI
10.1038/s44319-024-00132-7
Abstract
Ago2 differentially regulates oncogenic and tumor-suppressive miRNAs in cancer cells. This discrepancy suggests a secondary event regulating Ago2/miRNA action in a context-dependent manner. We show here that a positive charge of Ago2 K212, that is preserved by SIR2-mediated Ago2 deacetylation in cancer cells, is responsible for the direct interaction between Ago2 and Caveolin-1 (CAV1). Through this interaction, CAV1 sequesters Ago2 on the plasma membranes and regulates miRNA-mediated translational repression in a compartment-dependent manner. Ago2/CAV1 interaction plays a role in miRNA-mediated mRNA suppression and in miRNA release via extracellular vesicles (EVs) from tumors into the circulation, which can be used as a biomarker of tumor progression. Increased Ago2/CAV1 interaction with tumor progression promotes aggressive cancer behaviors, including metastasis. Ago2/CAV1 interaction acts as a secondary event in miRNA-mediated suppression and increases the complexity of miRNA actions in cancer.
Subjects
Argonaute-2
Caveolin-1
Exosome
Metastasis
miRNA
SDGs
Type
journal article