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A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates

Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 e...

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Autores principales: Lesbon, Jéssika Cristina Chagas, Garnica, Taismara Kustro, Xavier, Pedro Luiz Porfírio, Rochetti, Arina Lázaro, Reis, Rui Manuel, Müller, Susanne, Fukumasu, Heidge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570250/
https://www.ncbi.nlm.nih.gov/pubmed/36233212
http://dx.doi.org/10.3390/ijms231911911
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author Lesbon, Jéssika Cristina Chagas
Garnica, Taismara Kustro
Xavier, Pedro Luiz Porfírio
Rochetti, Arina Lázaro
Reis, Rui Manuel
Müller, Susanne
Fukumasu, Heidge
author_facet Lesbon, Jéssika Cristina Chagas
Garnica, Taismara Kustro
Xavier, Pedro Luiz Porfírio
Rochetti, Arina Lázaro
Reis, Rui Manuel
Müller, Susanne
Fukumasu, Heidge
author_sort Lesbon, Jéssika Cristina Chagas
collection PubMed
description Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells.
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spelling pubmed-95702502022-10-17 A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates Lesbon, Jéssika Cristina Chagas Garnica, Taismara Kustro Xavier, Pedro Luiz Porfírio Rochetti, Arina Lázaro Reis, Rui Manuel Müller, Susanne Fukumasu, Heidge Int J Mol Sci Article Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells. MDPI 2022-10-07 /pmc/articles/PMC9570250/ /pubmed/36233212 http://dx.doi.org/10.3390/ijms231911911 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
Lesbon, Jéssika Cristina Chagas
Garnica, Taismara Kustro
Xavier, Pedro Luiz Porfírio
Rochetti, Arina Lázaro
Reis, Rui Manuel
Müller, Susanne
Fukumasu, Heidge
A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates
title A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates
title_full A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates
title_fullStr A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates
title_full_unstemmed A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates
title_short A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates
title_sort screening of epigenetic therapeutic targets for non-small cell lung cancer reveals padi4 and kdm6b as promising candidates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570250/
https://www.ncbi.nlm.nih.gov/pubmed/36233212
http://dx.doi.org/10.3390/ijms231911911
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