Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells

UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the ai...

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Autores principales: Vitale, Daiana Luján, Caon, Ilaria, Parnigoni, Arianna, Sevic, Ina, Spinelli, Fiorella Mercedes, Icardi, Antonella, Passi, Alberto, Vigetti, Davide, Alaniz, Laura
Otros Autores: 0000-0001-5593-9101
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2023
Materias:
UDP-glucose dehydrogenase
Hyaluronan
Epirubicin
Drug resistance
Extracellular matrix
Breast cancer
Acceso en línea:http://repositorio.unnoba.edu.ar/xmlui/handle/23601/637
Aporte de:
Re DI Repositorio Digital UNNOBA de Universidad Nacional del Noroeste de la Provincia de Buenos Aires
id I103-R405-23601-637
record_format dspace
institution Universidad Nacional del Noroeste de la Provincia de Buenos Aires
institution_str I-103
repository_str R-405
collection Re DI Repositorio Digital UNNOBA
language Inglés
topic UDP-glucose dehydrogenase
Hyaluronan
Epirubicin
Drug resistance
Extracellular matrix
Breast cancer
spellingShingle UDP-glucose dehydrogenase
Hyaluronan
Epirubicin
Drug resistance
Extracellular matrix
Breast cancer
Vitale, Daiana Luján
Caon, Ilaria
Parnigoni, Arianna
Sevic, Ina
Spinelli, Fiorella Mercedes
Icardi, Antonella
Passi, Alberto
Vigetti, Davide
Alaniz, Laura
Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
topic_facet UDP-glucose dehydrogenase
Hyaluronan
Epirubicin
Drug resistance
Extracellular matrix
Breast cancer
description UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix.
author2 0000-0001-5593-9101
author_facet 0000-0001-5593-9101
Vitale, Daiana Luján
Caon, Ilaria
Parnigoni, Arianna
Sevic, Ina
Spinelli, Fiorella Mercedes
Icardi, Antonella
Passi, Alberto
Vigetti, Davide
Alaniz, Laura
format Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
author Vitale, Daiana Luján
Caon, Ilaria
Parnigoni, Arianna
Sevic, Ina
Spinelli, Fiorella Mercedes
Icardi, Antonella
Passi, Alberto
Vigetti, Davide
Alaniz, Laura
author_sort Vitale, Daiana Luján
title Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
title_short Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
title_full Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
title_fullStr Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
title_full_unstemmed Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
title_sort initial identification of udp-glucose dehydrogenase as a prognostic marker in breast cancer patients, which facilitates epirubicin resistance and regulates hyaluronan synthesis in mda-mb-231 cells
publishDate 2023
url http://repositorio.unnoba.edu.ar/xmlui/handle/23601/637
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spelling I103-R405-23601-6372025-10-21T21:14:40Z Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells Vitale, Daiana Luján Caon, Ilaria Parnigoni, Arianna Sevic, Ina Spinelli, Fiorella Mercedes Icardi, Antonella Passi, Alberto Vigetti, Davide Alaniz, Laura 0000-0001-5593-9101 0000-0003-3328-3089 0000-0002-6070-6078 UDP-glucose dehydrogenase Hyaluronan Epirubicin Drug resistance Extracellular matrix Breast cancer UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix. Fil: Vitale, Daiana Luján. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. CIT NOBA (UNNOBA-UNSADA-CONICET); Argentina. Fil: Caon, Ilaria. Università degli Studio dell’Insubria. Dipartimento di Medicina e Chirurgia; Italia. Fil: Parnigoni, Arianna. Università degli Studio dell’Insubria. Dipartimento di Medicina e Chirurgia; Italia. Fil: Sevic, Ina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Spinelli, Fiorella Mercedes. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Icardi, Antonella. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Icardi, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Passi, Alberto. Università degli Studio dell’Insubria. Dipartimento di Medicina e Chirurgia; Italia. Fil: Vigetti, Davide. Università degli Studio dell’Insubria. Dipartimento di Medicina e Chirurgia; Italia. Fil: Alaniz, Laura. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Alaniz, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Con referato 2023-12-04T20:05:51Z 2023-12-04T20:05:51Z 2021-02-09 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion Vitale D. L., Caon I., Parnigoni A., Sevic I., Spinelli F. M., Icardi A., Passi A., Vigetti D., Alaniz L. (2021). Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells. Biomolecules, 11(2), 246 2218-273X http://repositorio.unnoba.edu.ar/xmlui/handle/23601/637 eng eu-repo/grantAgreement/European Comission/H2020 RISE-MSCA Project/645,756/GLYCANC eu-repo/grantAgreement/UNNOBA/SIB 2019/0561-2019 https://doi.org/10.3390/biom11020246 info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf Biomolecules

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