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Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer

The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is s...

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Autores principales: Rodriguez-Aguayo, Cristian, Monroig, Paloma del C, Redis, Roxana S, Bayraktar, Emine, Almeida, Maria I, Ivan, Cristina, Fuentes-Mattei, Enrique, Rashed, Mohammed H, Chavez-Reyes, Arturo, Ozpolat, Bulent, Mitra, Rahul, Sood, Anil K, Calin, George A, Lopez-Berestein, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594916/
https://www.ncbi.nlm.nih.gov/pubmed/28904816
http://dx.doi.org/10.1038/celldisc.2017.29
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author Rodriguez-Aguayo, Cristian
Monroig, Paloma del C
Redis, Roxana S
Bayraktar, Emine
Almeida, Maria I
Ivan, Cristina
Fuentes-Mattei, Enrique
Rashed, Mohammed H
Chavez-Reyes, Arturo
Ozpolat, Bulent
Mitra, Rahul
Sood, Anil K
Calin, George A
Lopez-Berestein, Gabriel
author_facet Rodriguez-Aguayo, Cristian
Monroig, Paloma del C
Redis, Roxana S
Bayraktar, Emine
Almeida, Maria I
Ivan, Cristina
Fuentes-Mattei, Enrique
Rashed, Mohammed H
Chavez-Reyes, Arturo
Ozpolat, Bulent
Mitra, Rahul
Sood, Anil K
Calin, George A
Lopez-Berestein, Gabriel
author_sort Rodriguez-Aguayo, Cristian
collection PubMed
description The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene. The inhibition of miR-25-3p and miR-15a-5p decreased the proliferation, motility, invasiveness and angiogenic potential and increased apoptosis when combined with docetaxel. Alteration of this regulatory circuit causes poor overall survival outcome in ovarian cancer patients. These results highlight miR-15a-5p and miR-25-3p as key regulators of miR-18a-3p expression and its downstream target K-RAS, through direct modulation of hnRNPA1 expression. Our results demonstrate the therapeutic potential of inhibiting miR-25-3p and miR-15a-5p and the use of miR-18a-3p/KRAS ratio as a prominent outcome prognostic factor.
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spelling pubmed-55949162017-09-13 Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer Rodriguez-Aguayo, Cristian Monroig, Paloma del C Redis, Roxana S Bayraktar, Emine Almeida, Maria I Ivan, Cristina Fuentes-Mattei, Enrique Rashed, Mohammed H Chavez-Reyes, Arturo Ozpolat, Bulent Mitra, Rahul Sood, Anil K Calin, George A Lopez-Berestein, Gabriel Cell Discov Article The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene. The inhibition of miR-25-3p and miR-15a-5p decreased the proliferation, motility, invasiveness and angiogenic potential and increased apoptosis when combined with docetaxel. Alteration of this regulatory circuit causes poor overall survival outcome in ovarian cancer patients. These results highlight miR-15a-5p and miR-25-3p as key regulators of miR-18a-3p expression and its downstream target K-RAS, through direct modulation of hnRNPA1 expression. Our results demonstrate the therapeutic potential of inhibiting miR-25-3p and miR-15a-5p and the use of miR-18a-3p/KRAS ratio as a prominent outcome prognostic factor. Nature Publishing Group 2017-09-12 /pmc/articles/PMC5594916/ /pubmed/28904816 http://dx.doi.org/10.1038/celldisc.2017.29 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Rodriguez-Aguayo, Cristian
Monroig, Paloma del C
Redis, Roxana S
Bayraktar, Emine
Almeida, Maria I
Ivan, Cristina
Fuentes-Mattei, Enrique
Rashed, Mohammed H
Chavez-Reyes, Arturo
Ozpolat, Bulent
Mitra, Rahul
Sood, Anil K
Calin, George A
Lopez-Berestein, Gabriel
Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
title Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
title_full Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
title_fullStr Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
title_full_unstemmed Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
title_short Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
title_sort regulation of hnrnpa1 by micrornas controls the mir-18a–k-ras axis in chemotherapy-resistant ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594916/
https://www.ncbi.nlm.nih.gov/pubmed/28904816
http://dx.doi.org/10.1038/celldisc.2017.29
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