Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer

Abstract Mediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in brea...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Neha Nagpal, Shivani Sharma, Sourobh Maji, Giorgio Durante, Manuela Ferracin, Jitendra K. Thakur, Ritu Kulshreshtha
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a50771a56c64067824c83dae9b9aa4e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7a50771a56c64067824c83dae9b9aa4e
record_format	dspace
spelling	oai:doaj.org-article:7a50771a56c64067824c83dae9b9aa4e2021-12-02T15:08:11ZEssential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer10.1038/s41598-018-29546-92045-2322https://doaj.org/article/7a50771a56c64067824c83dae9b9aa4e2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29546-9https://doaj.org/toc/2045-2322Abstract Mediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in breast cancer and is a negative prognostic factor. The levels of several miRNAs (miR-100-5p, -191-5p, -193b-3p, -205-5p, -326, -422a and -425-5p) were found to be regulated by MED1. MED1 induces miR-191/425 cluster in an estrogen receptor-alpha (ER-α) dependent manner. Occupancy of MED1 on estrogen response elements (EREs) upstream of miR-191/425 cluster is estrogen and ER-α-dependent and ER-α-induced expression of these miRNAs is MED1-dependent. MED1 mediates induction of cell proliferation and migration and the genes associated with it (JUN, FOS, EGFR, VEGF, MMP1, and ERBB4) in breast cancer, which is abrogated when used together with miR-191-inhibition. Additionally, we show that MED1 also regulates the levels of direct miR-191 target genes such as SATB1, CDK6 and BDNF. Overall, the results show that MED1/ER-α/miR-191 axis promotes breast cancer cell proliferation and migration and may serve as a novel target for therapy.Neha NagpalShivani SharmaSourobh MajiGiorgio DuranteManuela FerracinJitendra K. ThakurRitu KulshreshthaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Neha Nagpal Shivani Sharma Sourobh Maji Giorgio Durante Manuela Ferracin Jitendra K. Thakur Ritu Kulshreshtha Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
description	Abstract Mediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in breast cancer and is a negative prognostic factor. The levels of several miRNAs (miR-100-5p, -191-5p, -193b-3p, -205-5p, -326, -422a and -425-5p) were found to be regulated by MED1. MED1 induces miR-191/425 cluster in an estrogen receptor-alpha (ER-α) dependent manner. Occupancy of MED1 on estrogen response elements (EREs) upstream of miR-191/425 cluster is estrogen and ER-α-dependent and ER-α-induced expression of these miRNAs is MED1-dependent. MED1 mediates induction of cell proliferation and migration and the genes associated with it (JUN, FOS, EGFR, VEGF, MMP1, and ERBB4) in breast cancer, which is abrogated when used together with miR-191-inhibition. Additionally, we show that MED1 also regulates the levels of direct miR-191 target genes such as SATB1, CDK6 and BDNF. Overall, the results show that MED1/ER-α/miR-191 axis promotes breast cancer cell proliferation and migration and may serve as a novel target for therapy.
format	article
author	Neha Nagpal Shivani Sharma Sourobh Maji Giorgio Durante Manuela Ferracin Jitendra K. Thakur Ritu Kulshreshtha
author_facet	Neha Nagpal Shivani Sharma Sourobh Maji Giorgio Durante Manuela Ferracin Jitendra K. Thakur Ritu Kulshreshtha
author_sort	Neha Nagpal
title	Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
title_short	Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
title_full	Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
title_fullStr	Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
title_full_unstemmed	Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
title_sort	essential role of med1 in the transcriptional regulation of er-dependent oncogenic mirnas in breast cancer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7a50771a56c64067824c83dae9b9aa4e
work_keys_str_mv	AT nehanagpal essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer AT shivanisharma essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer AT sourobhmaji essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer AT giorgiodurante essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer AT manuelaferracin essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer AT jitendrakthakur essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer AT ritukulshreshtha essentialroleofmed1inthetranscriptionalregulationoferdependentoncogenicmirnasinbreastcancer
_version_	1718388259857367040

Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer

Ejemplares similares