BRAFV600E Induction in Thyrocytes Triggers Important Changes in the miRNAs Content and the Populations of Extracellular Vesicles Released in Thyroid Tumor Microenvironment

Papillary thyroid cancer (PTC) is the most common endocrine malignancy for which diagnosis and recurrences still challenge clinicians. New perspectives to overcome these issues could come from the study of extracellular vesicle (EV) populations and content. Here, we aimed to elucidate the heterogene...

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Bibliographic Details
Published in:Biomedicines 2022-03, Vol.10 (4), p.755
Main Authors: Delcorte, Ophélie, Spourquet, Catherine, Lemoine, Pascale, Degosserie, Jonathan, Van Der Smissen, Patrick, Dauguet, Nicolas, Loriot, Axelle, Knauf, Jeffrey A., Gatto, Laurent, Marbaix, Etienne, Fagin, James A., Pierreux, Christophe E.
Format: Article
Language:English
Subjects:
Antibodies
BRAFV600E
Extracellular vesicles
Flow cytometry
Homogenization
Malignancy
Mechanical loading
Medical prognosis
MicroRNAs
miRNA
mouse model
Papillary thyroid cancer
PTC
Thyrocytes
Thyroid cancer
Tumor microenvironment
Tumors
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Summary:Papillary thyroid cancer (PTC) is the most common endocrine malignancy for which diagnosis and recurrences still challenge clinicians. New perspectives to overcome these issues could come from the study of extracellular vesicle (EV) populations and content. Here, we aimed to elucidate the heterogeneity of EVs circulating in the tumor and the changes in their microRNA content during cancer progression. Using a mouse model expressing BRAFV600E, we isolated and characterized EVs from thyroid tissue by ultracentrifugations and elucidated their microRNA content by small RNA sequencing. The cellular origin of EVs was investigated by ExoView and that of deregulated EV-microRNA by qPCR on FACS-sorted cell populations. We found that PTC released more EVs bearing epithelial and immune markers, as compared to the healthy thyroid, so that changes in EV-microRNAs abundance were mainly due to their deregulated expression in thyrocytes. Altogether, our work provides a full description of in vivo-derived EVs produced by, and within, normal and cancerous thyroid. We elucidated the global EV-microRNAs signature, the dynamic loading of microRNAs in EVs upon BRAFV600E induction, and their cellular origin. Finally, we propose that thyroid tumor-derived EV-microRNAs could support the establishment of a permissive immune microenvironment.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10040755