Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 17 March 2022 / Approved: 18 March 2022 / Online: 18 March 2022 (03:53:48 CET)

A peer-reviewed article of this Preprint also exists.

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. BRAFV600E Induction in Thyrocytes Triggers Important Changes in the miRNAs Content and the Populations of Extracellular Vesicles Released in Thyroid Tumor Microenvironment. Biomedicines 2022, 10, 755. 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. BRAFV600E Induction in Thyrocytes Triggers Important Changes in the miRNAs Content and the Populations of Extracellular Vesicles Released in Thyroid Tumor Microenvironment. Biomedicines 2022, 10, 755.

Journal reference: Biomedicines 2022, 10, 755
DOI: 10.3390/biomedicines10040755

Abstract

Papillary thyroid cancer (PTC) is the most common endocrine malignancy which diagnosis and recurrences still challenge clinicians. New perspectives to overcome those issues could come from the study of extracellular vesicles (EVs) populations and content. Here, we aimed to elucidate the heterogeneity of EVs circulating in 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. 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 healthy thyroid, and that changes in EV-microRNAs abundance were mainly due to their deregulated expression in thyrocytes. Pathway analysis showed that the more abundant EV-microRNAs could impact on immune processes. 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. Thyroid tumor-derived EV-microRNAs could support the establishment of a permissive immune microenvironment.

Keywords

thyroid cancer; PTC; BRAFV600E; mouse model; miRNA; extracellular vesicles; heterogeneity; se-quencing

Subject

BIOLOGY, Physiology

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