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miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines
Breast cancer (BC) is the most diagnosed carcinoma and the leading cause of cancer death in female over 100 countries. Thanks to the advance in therapeutic strategies, patients’ survival has improved. However, the lack of response to treatments and drug resistance are still a main concern, demanding...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689370/ https://www.ncbi.nlm.nih.gov/pubmed/33282861 http://dx.doi.org/10.3389/fcell.2020.579160 |
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author | Bandini, Erika Fanini, Francesca Vannini, Ivan Rossi, Tania Plousiou, Meropi Tumedei, Maria Maddalena Limarzi, Francesco Maltoni, Roberta Fabbri, Francesco Hrelia, Silvana Cho, William C. S. Fabbri, Muller |
author_facet | Bandini, Erika Fanini, Francesca Vannini, Ivan Rossi, Tania Plousiou, Meropi Tumedei, Maria Maddalena Limarzi, Francesco Maltoni, Roberta Fabbri, Francesco Hrelia, Silvana Cho, William C. S. Fabbri, Muller |
author_sort | Bandini, Erika |
collection | PubMed |
description | Breast cancer (BC) is the most diagnosed carcinoma and the leading cause of cancer death in female over 100 countries. Thanks to the advance in therapeutic strategies, patients’ survival has improved. However, the lack of response to treatments and drug resistance are still a main concern, demanding for new therapeutic approaches, in particular for the advanced stages of the disease. Androgen receptor (AR) is gaining increasing interest as a fourth targetable receptor in BC, however, its regulation in BC cells is still poorly understood. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Here, we identified miR-9-5p as an inhibitor of AR expression, we validated the inverse correlation between miR-9-5p and AR in primary BC samples and we further identified a feedback loop in which androgen agonists of AR up-regulate miR-9-5p. We also provided evidence that miR-9-5p elicits anti-proliferative effects in BC cell lines regardless of their estrogen receptor status. Finally, we showed that miR-9-5p can revert AR-downstream signaling even in presence of AR-agonists, highlighting the role of this miR in the hormonal response of BC. In conclusion, this study supports the role of miR-9-5p as an anti-proliferative miR in BC and as a central modulator of AR-signaling response to circulating androgens in BC. |
format | Online Article Text |
id | pubmed-7689370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76893702020-12-04 miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines Bandini, Erika Fanini, Francesca Vannini, Ivan Rossi, Tania Plousiou, Meropi Tumedei, Maria Maddalena Limarzi, Francesco Maltoni, Roberta Fabbri, Francesco Hrelia, Silvana Cho, William C. S. Fabbri, Muller Front Cell Dev Biol Cell and Developmental Biology Breast cancer (BC) is the most diagnosed carcinoma and the leading cause of cancer death in female over 100 countries. Thanks to the advance in therapeutic strategies, patients’ survival has improved. However, the lack of response to treatments and drug resistance are still a main concern, demanding for new therapeutic approaches, in particular for the advanced stages of the disease. Androgen receptor (AR) is gaining increasing interest as a fourth targetable receptor in BC, however, its regulation in BC cells is still poorly understood. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Here, we identified miR-9-5p as an inhibitor of AR expression, we validated the inverse correlation between miR-9-5p and AR in primary BC samples and we further identified a feedback loop in which androgen agonists of AR up-regulate miR-9-5p. We also provided evidence that miR-9-5p elicits anti-proliferative effects in BC cell lines regardless of their estrogen receptor status. Finally, we showed that miR-9-5p can revert AR-downstream signaling even in presence of AR-agonists, highlighting the role of this miR in the hormonal response of BC. In conclusion, this study supports the role of miR-9-5p as an anti-proliferative miR in BC and as a central modulator of AR-signaling response to circulating androgens in BC. Frontiers Media S.A. 2020-11-12 /pmc/articles/PMC7689370/ /pubmed/33282861 http://dx.doi.org/10.3389/fcell.2020.579160 Text en Copyright © 2020 Bandini, Fanini, Vannini, Rossi, Plousiou, Tumedei, Limarzi, Maltoni, Fabbri, Hrelia, Cho and Fabbri. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Bandini, Erika Fanini, Francesca Vannini, Ivan Rossi, Tania Plousiou, Meropi Tumedei, Maria Maddalena Limarzi, Francesco Maltoni, Roberta Fabbri, Francesco Hrelia, Silvana Cho, William C. S. Fabbri, Muller miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines |
title | miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines |
title_full | miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines |
title_fullStr | miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines |
title_full_unstemmed | miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines |
title_short | miR-9-5p as a Regulator of the Androgen Receptor Pathway in Breast Cancer Cell Lines |
title_sort | mir-9-5p as a regulator of the androgen receptor pathway in breast cancer cell lines |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689370/ https://www.ncbi.nlm.nih.gov/pubmed/33282861 http://dx.doi.org/10.3389/fcell.2020.579160 |
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