BRAF(V600E) induction in thyrocytes triggers important changes in the miRNAs content and the populations of extracellular vesicles released in thyroid tumor microenvironment Journal Article


Authors: Delcorte, O.; Spourquet, C.; Lemoine, P.; Degosserie, J.; Van Der Smissen, P.; Dauguet, N.; Loriot, A.; Knauf, J. A.; Gatto, L.; Marbaix, E.; Fagin, J. A.; Pierreux, C. E.
Article Title: BRAF(V600E) induction in thyrocytes triggers important changes in the miRNAs content and the populations of extracellular vesicles released in thyroid tumor microenvironment
Abstract: 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: thyroid cancer; sequencing; mouse model; heterogeneity; mirna; brafv600e; ptc; extracellular vesicles
Journal Title: Biomedicines
Volume: 10
Issue: 4
ISSN: 2227-9059
Publisher: MDPI  
Date Published: 2022-04-01
Start Page: 755
Language: English
DOI: 10.3390/biomedicines10040755
PROVIDER: scopus
PMCID: PMC9029139
PUBMED: 35453506
DOI/URL:
Notes: Article -- Export Date: 2 May 2022 -- Source: Scopus
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  1. James A Fagin
    180 Fagin
  2. Jeffrey A Knauf
    61 Knauf