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MicroRNA regulation of progesterone receptor in breast cancer

Hormone receptor status is of significant value when deciding on anti-estrogenic adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER) regulation was intensively studied, the regulation of progesterone receptor (PR) levels has not been extensively investigated. MicroRNAs (...

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Autores principales: Gilam, Avital, Shai, Ayelet, Ashkenazi, Itamar, Sarid, Liat Appel, Drobot, Assi, Bickel, Amitai, Shomron, Noam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432230/
https://www.ncbi.nlm.nih.gov/pubmed/28404930
http://dx.doi.org/10.18632/oncotarget.15657
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author Gilam, Avital
Shai, Ayelet
Ashkenazi, Itamar
Sarid, Liat Appel
Drobot, Assi
Bickel, Amitai
Shomron, Noam
author_facet Gilam, Avital
Shai, Ayelet
Ashkenazi, Itamar
Sarid, Liat Appel
Drobot, Assi
Bickel, Amitai
Shomron, Noam
author_sort Gilam, Avital
collection PubMed
description Hormone receptor status is of significant value when deciding on anti-estrogenic adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER) regulation was intensively studied, the regulation of progesterone receptor (PR) levels has not been extensively investigated. MicroRNAs (miRNAs, miRs) are post-transcriptional negative regulators of gene expression involved in diverse cellular processes. The aim of this study was to identify miRNAs that regulate PR in breast cancer. We mapped potential miRNA binding sites for miR-181a, miR-23a and miR-26b on PR mRNA and demonstrated a direct regulation of PR by these three miRNAs by in-vitro Luciferase binding assays. Over-expression of each miRNA in MCF-7 cells resulted in a reduction in the expression levels of PR mRNA. Then, expression levels of these miRNAs were measured in Formalin-Fixed, Paraffin-Embedded (FFPE) samples of 29 ER-positive breast cancer tumors and adjacent normal breast tissues. A significant reciprocal correlation between PR mRNA and the miRNA levels were identified suggesting a role for miR-181a, miR-23a and miR-26b in PR regulation in breast cancer. Moreover, the average expression fold-changes of the three miRNAs between cancerous and normal tissues displayed an opposite trend when analyzing according to Immuno-histochemistry(IHC) status. Furthermore, miR-181a and miR-26b were found to be over-expressed in most tumor tissues supporting their role in ER-positive breast cancer development. We conclude that miR-181a, miR-23a and miR-26b act as negative regulators of PR expression in ER-positive breast cancer. The diagnostic and prognostic potential of these miRNAs in breast cancer should be further evaluated.
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spelling pubmed-54322302017-05-17 MicroRNA regulation of progesterone receptor in breast cancer Gilam, Avital Shai, Ayelet Ashkenazi, Itamar Sarid, Liat Appel Drobot, Assi Bickel, Amitai Shomron, Noam Oncotarget Research Paper Hormone receptor status is of significant value when deciding on anti-estrogenic adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER) regulation was intensively studied, the regulation of progesterone receptor (PR) levels has not been extensively investigated. MicroRNAs (miRNAs, miRs) are post-transcriptional negative regulators of gene expression involved in diverse cellular processes. The aim of this study was to identify miRNAs that regulate PR in breast cancer. We mapped potential miRNA binding sites for miR-181a, miR-23a and miR-26b on PR mRNA and demonstrated a direct regulation of PR by these three miRNAs by in-vitro Luciferase binding assays. Over-expression of each miRNA in MCF-7 cells resulted in a reduction in the expression levels of PR mRNA. Then, expression levels of these miRNAs were measured in Formalin-Fixed, Paraffin-Embedded (FFPE) samples of 29 ER-positive breast cancer tumors and adjacent normal breast tissues. A significant reciprocal correlation between PR mRNA and the miRNA levels were identified suggesting a role for miR-181a, miR-23a and miR-26b in PR regulation in breast cancer. Moreover, the average expression fold-changes of the three miRNAs between cancerous and normal tissues displayed an opposite trend when analyzing according to Immuno-histochemistry(IHC) status. Furthermore, miR-181a and miR-26b were found to be over-expressed in most tumor tissues supporting their role in ER-positive breast cancer development. We conclude that miR-181a, miR-23a and miR-26b act as negative regulators of PR expression in ER-positive breast cancer. The diagnostic and prognostic potential of these miRNAs in breast cancer should be further evaluated. Impact Journals LLC 2017-02-23 /pmc/articles/PMC5432230/ /pubmed/28404930 http://dx.doi.org/10.18632/oncotarget.15657 Text en Copyright: © 2017 Gilam et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Gilam, Avital
Shai, Ayelet
Ashkenazi, Itamar
Sarid, Liat Appel
Drobot, Assi
Bickel, Amitai
Shomron, Noam
MicroRNA regulation of progesterone receptor in breast cancer
title MicroRNA regulation of progesterone receptor in breast cancer
title_full MicroRNA regulation of progesterone receptor in breast cancer
title_fullStr MicroRNA regulation of progesterone receptor in breast cancer
title_full_unstemmed MicroRNA regulation of progesterone receptor in breast cancer
title_short MicroRNA regulation of progesterone receptor in breast cancer
title_sort microrna regulation of progesterone receptor in breast cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432230/
https://www.ncbi.nlm.nih.gov/pubmed/28404930
http://dx.doi.org/10.18632/oncotarget.15657
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