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Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology

Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transc...

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Autores principales: Maldonado, Edio, Morales-Pison, Sebastian, Urbina, Fabiola, Jara, Lilian, Solari, Aldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871970/
https://www.ncbi.nlm.nih.gov/pubmed/35205279
http://dx.doi.org/10.3390/genes13020234
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author Maldonado, Edio
Morales-Pison, Sebastian
Urbina, Fabiola
Jara, Lilian
Solari, Aldo
author_facet Maldonado, Edio
Morales-Pison, Sebastian
Urbina, Fabiola
Jara, Lilian
Solari, Aldo
author_sort Maldonado, Edio
collection PubMed
description Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly through the MED1 subunit, since estrogen receptor (ER) can interact with MED1 by specific protein–protein interactions; therefore, MED1 plays a fundamental role in ER-positive breast cancer (BC) etiology. Additionally, other MED subunits also play a role in BC etiology. On the other hand, microRNAs (miRNAs) are a family of small non-coding RNAs, which can regulate gene expression at the post-transcriptional level by binding in a sequence-specific fashion at the 3′ UTR of the messenger RNA. The miRNAs are also important factors that influence oncogenic signaling in BC by acting as both tumor suppressors and oncogenes. Moreover, miRNAs are involved in endocrine therapy resistance of BC, specifically to tamoxifen, a drug that is used to target ER signaling. In metazoans, very little is known about the transcriptional regulation of miRNA by the MED complex and less about the transcriptional regulation of miRNAs involved in BC initiation and progression. Recently, it has been shown that MED1 is able to regulate the transcription of the ER-dependent miR-191/425 cluster promoting BC cell proliferation and migration. In this review, we will discuss the role of MED1 transcriptional coactivator in the etiology of BC and in endocrine therapy-resistance of BC and also the contribution of other MED subunits to BC development, progression and metastasis. Lastly, we identified miRNAs that potentially can regulate the expression of MED subunits.
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spelling pubmed-88719702022-02-25 Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology Maldonado, Edio Morales-Pison, Sebastian Urbina, Fabiola Jara, Lilian Solari, Aldo Genes (Basel) Review Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly through the MED1 subunit, since estrogen receptor (ER) can interact with MED1 by specific protein–protein interactions; therefore, MED1 plays a fundamental role in ER-positive breast cancer (BC) etiology. Additionally, other MED subunits also play a role in BC etiology. On the other hand, microRNAs (miRNAs) are a family of small non-coding RNAs, which can regulate gene expression at the post-transcriptional level by binding in a sequence-specific fashion at the 3′ UTR of the messenger RNA. The miRNAs are also important factors that influence oncogenic signaling in BC by acting as both tumor suppressors and oncogenes. Moreover, miRNAs are involved in endocrine therapy resistance of BC, specifically to tamoxifen, a drug that is used to target ER signaling. In metazoans, very little is known about the transcriptional regulation of miRNA by the MED complex and less about the transcriptional regulation of miRNAs involved in BC initiation and progression. Recently, it has been shown that MED1 is able to regulate the transcription of the ER-dependent miR-191/425 cluster promoting BC cell proliferation and migration. In this review, we will discuss the role of MED1 transcriptional coactivator in the etiology of BC and in endocrine therapy-resistance of BC and also the contribution of other MED subunits to BC development, progression and metastasis. Lastly, we identified miRNAs that potentially can regulate the expression of MED subunits. MDPI 2022-01-26 /pmc/articles/PMC8871970/ /pubmed/35205279 http://dx.doi.org/10.3390/genes13020234 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Maldonado, Edio
Morales-Pison, Sebastian
Urbina, Fabiola
Jara, Lilian
Solari, Aldo
Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
title Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
title_full Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
title_fullStr Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
title_full_unstemmed Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
title_short Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology
title_sort role of the mediator complex and micrornas in breast cancer etiology
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871970/
https://www.ncbi.nlm.nih.gov/pubmed/35205279
http://dx.doi.org/10.3390/genes13020234
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