hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells

Jennifer Pérez-Boza, Amandine Boeckx, Michele Lion, Franck Dequiedt, Ingrid Struman

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs.
Original languageEnglish
JournalCellular and Molecular Life Sciences
DOIs
Publication statusPublished - 2020
Externally publishedYes

Cite this

Pérez-Boza, Jennifer ; Boeckx, Amandine ; Lion, Michele ; Dequiedt, Franck ; Struman, Ingrid. / hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells. In: Cellular and Molecular Life Sciences. 2020.
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title = "hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells",
abstract = "The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs.",
author = "Jennifer P{\'e}rez-Boza and Amandine Boeckx and Michele Lion and Franck Dequiedt and Ingrid Struman",
year = "2020",
doi = "10.1007/s00018-019-03425-6",
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journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
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hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells. / Pérez-Boza, Jennifer; Boeckx, Amandine; Lion, Michele; Dequiedt, Franck; Struman, Ingrid.

In: Cellular and Molecular Life Sciences, 2020.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells

AU - Pérez-Boza, Jennifer

AU - Boeckx, Amandine

AU - Lion, Michele

AU - Dequiedt, Franck

AU - Struman, Ingrid

PY - 2020

Y1 - 2020

N2 - The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs.

AB - The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs.

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