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Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels

Chemoresistance is a major problem in the therapeutic management of pancreatic cancer, concurring to poor clinical outcome. A number of mechanisms have been proposed to explain resistance to gemcitabine, a standard of care for this malignancy, among which is included aberrant miRNA expression. In th...

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Autores principales: Panebianco, Concetta, Trivieri, Nadia, Villani, Annacandida, Terracciano, Fulvia, Latiano, Tiziana Pia, Potenza, Adele, Perri, Francesco, Binda, Elena, Pazienza, Valerio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146031/
https://www.ncbi.nlm.nih.gov/pubmed/33925948
http://dx.doi.org/10.3390/biom11050639
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author Panebianco, Concetta
Trivieri, Nadia
Villani, Annacandida
Terracciano, Fulvia
Latiano, Tiziana Pia
Potenza, Adele
Perri, Francesco
Binda, Elena
Pazienza, Valerio
author_facet Panebianco, Concetta
Trivieri, Nadia
Villani, Annacandida
Terracciano, Fulvia
Latiano, Tiziana Pia
Potenza, Adele
Perri, Francesco
Binda, Elena
Pazienza, Valerio
author_sort Panebianco, Concetta
collection PubMed
description Chemoresistance is a major problem in the therapeutic management of pancreatic cancer, concurring to poor clinical outcome. A number of mechanisms have been proposed to explain resistance to gemcitabine, a standard of care for this malignancy, among which is included aberrant miRNA expression. In the current study, we investigated the role of miR-217, which is strongly down-regulated in cancerous, compared to normal, pancreatic tissues or cells, in sensitizing human pancreatic cancer cell lines to this drug. The low expression of miR-217 in pancreatic cancer patients was confirmed in two gene expression datasets (GSE41372 and GSE60980), and the prognostic value of two target genes (ANLN and TRPS1), was estimated on clinical data from the Tumor Cancer Genome Atlas (TCGA). Transfecting miR-217 mimic in pancreatic cancer cells reduced viability, enhanced apoptosis, and affected cell cycle by promoting a S phase arrest in gemcitabine-treated cells. Moreover, in drug-exposed cells subjected to miR-217 forced expression, a down-regulation for several genes involved in cancer drug resistance was observed, many of which are cell cycle regulators, such as CCND1, CCNE1, CDK2, CDKN1A, CDKN1B, while others, such as ARNT, BRCA1, BRCA2, ELK1, EGFR, ERBB4, and RARA are involved in proliferation and cell cycle progression. Our results support the notion that miR-217 enhances pancreatic cancer sensitivity to gemcitabine, mainly impairing cell cycle progression.
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spelling pubmed-81460312021-05-26 Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels Panebianco, Concetta Trivieri, Nadia Villani, Annacandida Terracciano, Fulvia Latiano, Tiziana Pia Potenza, Adele Perri, Francesco Binda, Elena Pazienza, Valerio Biomolecules Article Chemoresistance is a major problem in the therapeutic management of pancreatic cancer, concurring to poor clinical outcome. A number of mechanisms have been proposed to explain resistance to gemcitabine, a standard of care for this malignancy, among which is included aberrant miRNA expression. In the current study, we investigated the role of miR-217, which is strongly down-regulated in cancerous, compared to normal, pancreatic tissues or cells, in sensitizing human pancreatic cancer cell lines to this drug. The low expression of miR-217 in pancreatic cancer patients was confirmed in two gene expression datasets (GSE41372 and GSE60980), and the prognostic value of two target genes (ANLN and TRPS1), was estimated on clinical data from the Tumor Cancer Genome Atlas (TCGA). Transfecting miR-217 mimic in pancreatic cancer cells reduced viability, enhanced apoptosis, and affected cell cycle by promoting a S phase arrest in gemcitabine-treated cells. Moreover, in drug-exposed cells subjected to miR-217 forced expression, a down-regulation for several genes involved in cancer drug resistance was observed, many of which are cell cycle regulators, such as CCND1, CCNE1, CDK2, CDKN1A, CDKN1B, while others, such as ARNT, BRCA1, BRCA2, ELK1, EGFR, ERBB4, and RARA are involved in proliferation and cell cycle progression. Our results support the notion that miR-217 enhances pancreatic cancer sensitivity to gemcitabine, mainly impairing cell cycle progression. MDPI 2021-04-26 /pmc/articles/PMC8146031/ /pubmed/33925948 http://dx.doi.org/10.3390/biom11050639 Text en © 2021 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
Panebianco, Concetta
Trivieri, Nadia
Villani, Annacandida
Terracciano, Fulvia
Latiano, Tiziana Pia
Potenza, Adele
Perri, Francesco
Binda, Elena
Pazienza, Valerio
Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
title Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
title_full Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
title_fullStr Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
title_full_unstemmed Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
title_short Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
title_sort improving gemcitabine sensitivity in pancreatic cancer cells by restoring mirna-217 levels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146031/
https://www.ncbi.nlm.nih.gov/pubmed/33925948
http://dx.doi.org/10.3390/biom11050639
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