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MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients

The standard clinical management of locally advanced rectal cancer (LARC) patients includes neoadjuvant 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by mesorectal excision. MicroRNA (miR)-19b expression levels in LARC biopsies obtained from initial colonoscopy have recently been iden...

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Autores principales: Santos, Andrea, Cristóbal, Ion, Rubio, Jaime, Caramés, Cristina, Luque, Melani, Sanz-Álvarez, Marta, Zazo, Sandra, Madoz-Gúrpide, Juan, Rojo, Federico, García-Foncillas, Jesus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604503/
https://www.ncbi.nlm.nih.gov/pubmed/36293302
http://dx.doi.org/10.3390/ijms232012447
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author Santos, Andrea
Cristóbal, Ion
Rubio, Jaime
Caramés, Cristina
Luque, Melani
Sanz-Álvarez, Marta
Zazo, Sandra
Madoz-Gúrpide, Juan
Rojo, Federico
García-Foncillas, Jesus
author_facet Santos, Andrea
Cristóbal, Ion
Rubio, Jaime
Caramés, Cristina
Luque, Melani
Sanz-Álvarez, Marta
Zazo, Sandra
Madoz-Gúrpide, Juan
Rojo, Federico
García-Foncillas, Jesus
author_sort Santos, Andrea
collection PubMed
description The standard clinical management of locally advanced rectal cancer (LARC) patients includes neoadjuvant 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by mesorectal excision. MicroRNA (miR)-19b expression levels in LARC biopsies obtained from initial colonoscopy have recently been identified as independent predictors of both patient outcome and pathological response to preoperative CRT in this disease. Moreover, it has been discovered that this miR increases its expression in 5-FU resistant colon cancer cells after 5-FU exposure. Despite the fact that these observations suggest a functional role of miR-19b modulating 5-FU response of LARC cells, this issue still remains to be clarified. Here, we show that downregulation of miR-19b enhances the antitumor effects of 5-FU treatment. Moreover, ectopic miR-19b modulation was able to restore sensitivity to 5-FU treatment using an acquired resistant model to this compound. Notably, we also evaluated the potential clinical impact of miR-19b as a predictive marker of disease progression after tumor surgery resection in LARC patients, observing that miR-19b overexpression significantly anticipates patient recurrence in our cohort (p = 0.002). Altogether, our findings demonstrate the functional role of miR-19b in the progressively decreasing sensitivity to 5-FU treatment and its potential usefulness as a therapeutic target to overcome 5-FU resistance, as well as its clinical impact as predictor of tumor progression and relapse.
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spelling pubmed-96045032022-10-27 MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients Santos, Andrea Cristóbal, Ion Rubio, Jaime Caramés, Cristina Luque, Melani Sanz-Álvarez, Marta Zazo, Sandra Madoz-Gúrpide, Juan Rojo, Federico García-Foncillas, Jesus Int J Mol Sci Article The standard clinical management of locally advanced rectal cancer (LARC) patients includes neoadjuvant 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by mesorectal excision. MicroRNA (miR)-19b expression levels in LARC biopsies obtained from initial colonoscopy have recently been identified as independent predictors of both patient outcome and pathological response to preoperative CRT in this disease. Moreover, it has been discovered that this miR increases its expression in 5-FU resistant colon cancer cells after 5-FU exposure. Despite the fact that these observations suggest a functional role of miR-19b modulating 5-FU response of LARC cells, this issue still remains to be clarified. Here, we show that downregulation of miR-19b enhances the antitumor effects of 5-FU treatment. Moreover, ectopic miR-19b modulation was able to restore sensitivity to 5-FU treatment using an acquired resistant model to this compound. Notably, we also evaluated the potential clinical impact of miR-19b as a predictive marker of disease progression after tumor surgery resection in LARC patients, observing that miR-19b overexpression significantly anticipates patient recurrence in our cohort (p = 0.002). Altogether, our findings demonstrate the functional role of miR-19b in the progressively decreasing sensitivity to 5-FU treatment and its potential usefulness as a therapeutic target to overcome 5-FU resistance, as well as its clinical impact as predictor of tumor progression and relapse. MDPI 2022-10-18 /pmc/articles/PMC9604503/ /pubmed/36293302 http://dx.doi.org/10.3390/ijms232012447 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 Article
Santos, Andrea
Cristóbal, Ion
Rubio, Jaime
Caramés, Cristina
Luque, Melani
Sanz-Álvarez, Marta
Zazo, Sandra
Madoz-Gúrpide, Juan
Rojo, Federico
García-Foncillas, Jesus
MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients
title MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients
title_full MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients
title_fullStr MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients
title_full_unstemmed MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients
title_short MicroRNA-19b Plays a Key Role in 5-Fluorouracil Resistance and Predicts Tumor Progression in Locally Advanced Rectal Cancer Patients
title_sort microrna-19b plays a key role in 5-fluorouracil resistance and predicts tumor progression in locally advanced rectal cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604503/
https://www.ncbi.nlm.nih.gov/pubmed/36293302
http://dx.doi.org/10.3390/ijms232012447
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