Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the...

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Autores principales:	Olga E. Andreeva, Danila V. Sorokin, Ekaterina I. Mikhaevich, Irina V. Bure, Yuri Y. Shchegolev, Marina V. Nemtsova, Margarita V. Gudkova, Alexander M. Scherbakov, Mikhail A. Krasil’nikov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	signalling pathways tamoxifen resistance exosomes miRNA (microRNA) breast cancer oestrogen receptor Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/c6197227fafb41d98d68afba5eda1784
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spelling	oai:doaj.org-article:c6197227fafb41d98d68afba5eda17842021-11-11T18:37:49ZTowards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance10.3390/molecules262166611420-3049https://doaj.org/article/c6197227fafb41d98d68afba5eda17842021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6661https://doaj.org/toc/1420-3049Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.Olga E. AndreevaDanila V. SorokinEkaterina I. MikhaevichIrina V. BureYuri Y. ShchegolevMarina V. NemtsovaMargarita V. GudkovaAlexander M. ScherbakovMikhail A. Krasil’nikovMDPI AGarticlesignalling pathwaystamoxifen resistanceexosomesmiRNA (microRNA)breast canceroestrogen receptorOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6661, p 6661 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	signalling pathways tamoxifen resistance exosomes miRNA (microRNA) breast cancer oestrogen receptor Organic chemistry QD241-441
spellingShingle	signalling pathways tamoxifen resistance exosomes miRNA (microRNA) breast cancer oestrogen receptor Organic chemistry QD241-441 Olga E. Andreeva Danila V. Sorokin Ekaterina I. Mikhaevich Irina V. Bure Yuri Y. Shchegolev Marina V. Nemtsova Margarita V. Gudkova Alexander M. Scherbakov Mikhail A. Krasil’nikov Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance
description	Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.
format	article
author	Olga E. Andreeva Danila V. Sorokin Ekaterina I. Mikhaevich Irina V. Bure Yuri Y. Shchegolev Marina V. Nemtsova Margarita V. Gudkova Alexander M. Scherbakov Mikhail A. Krasil’nikov
author_facet	Olga E. Andreeva Danila V. Sorokin Ekaterina I. Mikhaevich Irina V. Bure Yuri Y. Shchegolev Marina V. Nemtsova Margarita V. Gudkova Alexander M. Scherbakov Mikhail A. Krasil’nikov
author_sort	Olga E. Andreeva
title	Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance
title_short	Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance
title_full	Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance
title_fullStr	Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance
title_full_unstemmed	Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance
title_sort	towards unravelling the role of erα-targeting mirnas in the exosome-mediated transferring of the hormone resistance
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c6197227fafb41d98d68afba5eda1784
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Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

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