The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells

Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by c...

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Main Authors: Charlotte Orre, Xavier Dieu, Jordan Guillon, Naïg Gueguen, Seyedeh Tayebeh Ahmadpour, Jean-François Dumas, Salim Khiati, Pascal Reynier, Guy Lenaers, Olivier Coqueret, Arnaud Chevrollier, Delphine Mirebeau-Prunier, Valérie Desquiret-Dumas
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/10/11/1156
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author Charlotte Orre
Xavier Dieu
Jordan Guillon
Naïg Gueguen
Seyedeh Tayebeh Ahmadpour
Jean-François Dumas
Salim Khiati
Pascal Reynier
Guy Lenaers
Olivier Coqueret
Arnaud Chevrollier
Delphine Mirebeau-Prunier
Valérie Desquiret-Dumas
author_facet Charlotte Orre
Xavier Dieu
Jordan Guillon
Naïg Gueguen
Seyedeh Tayebeh Ahmadpour
Jean-François Dumas
Salim Khiati
Pascal Reynier
Guy Lenaers
Olivier Coqueret
Arnaud Chevrollier
Delphine Mirebeau-Prunier
Valérie Desquiret-Dumas
author_sort Charlotte Orre
collection DOAJ
description Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecules (lncRNAs) have emerged as important regulators of cellular metabolic orientation. In the present study, we addressed the role of the long non-coding RNA molecule (lncRNA) SAMMSON on the metabolic reprogramming and chemoresistance of MCF-7 breast cancer cells resistant to doxorubicin (MCF-7dox). Our results showed an overexpression of SAMMSON in MCF-7dox compared to doxorubicin-sensitive cells (MCF-7). Silencing of SAMMSON expression by siRNA in MCF-7dox cells resulted in a metabolic rewiring with improvement of oxidative metabolism, decreased mitochondrial ROS production, increased mitochondrial replication, transcription and translation and an attenuation of chemoresistance. These results highlight the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in breast cancer cells. Thus, targeting SAMMSON expression levels represents a promising therapeutic route to circumvent doxorubicin resistance in breast cancers.
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spelling doaj.art-98353807760346749bdef56025f7443a2023-11-22T22:28:10ZengMDPI AGBiology2079-77372021-11-011011115610.3390/biology10111156The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer CellsCharlotte Orre0Xavier Dieu1Jordan Guillon2Naïg Gueguen3Seyedeh Tayebeh Ahmadpour4Jean-François Dumas5Salim Khiati6Pascal Reynier7Guy Lenaers8Olivier Coqueret9Arnaud Chevrollier10Delphine Mirebeau-Prunier11Valérie Desquiret-Dumas12Mitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FrancePaul Papin ICO Cancer Center, CRCINA, INSERM, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceNutrition, Croissance et Cancer, Inserm UMR1069, Université de Tours, F-37032 Tours, FranceNutrition, Croissance et Cancer, Inserm UMR1069, Université de Tours, F-37032 Tours, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FrancePaul Papin ICO Cancer Center, CRCINA, INSERM, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceMitolab Team, Inserm U1083, CNRS 6015, Mito Vasc Institute, SFR ICAT, Angers University, F-49000 Angers, FranceDespite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecules (lncRNAs) have emerged as important regulators of cellular metabolic orientation. In the present study, we addressed the role of the long non-coding RNA molecule (lncRNA) SAMMSON on the metabolic reprogramming and chemoresistance of MCF-7 breast cancer cells resistant to doxorubicin (MCF-7dox). Our results showed an overexpression of SAMMSON in MCF-7dox compared to doxorubicin-sensitive cells (MCF-7). Silencing of SAMMSON expression by siRNA in MCF-7dox cells resulted in a metabolic rewiring with improvement of oxidative metabolism, decreased mitochondrial ROS production, increased mitochondrial replication, transcription and translation and an attenuation of chemoresistance. These results highlight the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in breast cancer cells. Thus, targeting SAMMSON expression levels represents a promising therapeutic route to circumvent doxorubicin resistance in breast cancers.https://www.mdpi.com/2079-7737/10/11/1156breast cancermitochondriametabolismcomplex Ilong non-coding RNASAMMSON
spellingShingle Charlotte Orre
Xavier Dieu
Jordan Guillon
Naïg Gueguen
Seyedeh Tayebeh Ahmadpour
Jean-François Dumas
Salim Khiati
Pascal Reynier
Guy Lenaers
Olivier Coqueret
Arnaud Chevrollier
Delphine Mirebeau-Prunier
Valérie Desquiret-Dumas
The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells
Biology
breast cancer
mitochondria
metabolism
complex I
long non-coding RNA
SAMMSON
title The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells
title_full The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells
title_fullStr The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells
title_full_unstemmed The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells
title_short The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells
title_sort long non coding rna sammson is a regulator of chemosensitivity and metabolic orientation in mcf 7 doxorubicin resistant breast cancer cells
topic breast cancer
mitochondria
metabolism
complex I
long non-coding RNA
SAMMSON
url https://www.mdpi.com/2079-7737/10/11/1156
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