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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doaj-572bed7fc49043a0909824d4257d9e3f2021-04-26T23:02:47ZengMDPI AGBiomolecules2218-273X2021-04-011163963910.3390/biom11050639Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 LevelsConcetta Panebianco0Nadia Trivieri1Annacandida Villani2Fulvia Terracciano3Tiziana Pia Latiano4Adele Potenza5Francesco Perri6Elena Binda7Valerio Pazienza8Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyCancer Stem Cell Unit, Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyGastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyGastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyOncology Unit Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyDietetic and Clinical Nutrition Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyGastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyCancer Stem Cell Unit, Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyGastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyChemoresistance 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 <i>CCND1</i>,<i> CCNE1</i>,<i> CDK2</i>,<i> CDKN1A</i>,<i> CDKN1B</i>, while others, such as <i>ARNT, BRCA1, BRCA2, ELK1, EGFR, ERBB4,</i> and <i>RARA</i> 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.https://www.mdpi.com/2218-273X/11/5/639miRNApancreatic cancerchemoresistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Concetta Panebianco Nadia Trivieri Annacandida Villani Fulvia Terracciano Tiziana Pia Latiano Adele Potenza Francesco Perri Elena Binda Valerio Pazienza |
spellingShingle |
Concetta Panebianco Nadia Trivieri Annacandida Villani Fulvia Terracciano Tiziana Pia Latiano Adele Potenza Francesco Perri Elena Binda Valerio Pazienza Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels Biomolecules miRNA pancreatic cancer chemoresistance |
author_facet |
Concetta Panebianco Nadia Trivieri Annacandida Villani Fulvia Terracciano Tiziana Pia Latiano Adele Potenza Francesco Perri Elena Binda Valerio Pazienza |
author_sort |
Concetta Panebianco |
title |
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_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_sort |
improving gemcitabine sensitivity in pancreatic cancer cells by restoring mirna-217 levels |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-04-01 |
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 <i>CCND1</i>,<i> CCNE1</i>,<i> CDK2</i>,<i> CDKN1A</i>,<i> CDKN1B</i>, while others, such as <i>ARNT, BRCA1, BRCA2, ELK1, EGFR, ERBB4,</i> and <i>RARA</i> 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. |
topic |
miRNA pancreatic cancer chemoresistance |
url |
https://www.mdpi.com/2218-273X/11/5/639 |
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