Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance

Abstract This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation w...

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Autores principales:	A K M Nawshad Hossian, Fatema Tuz Zahra, Sagun Poudel, Camille F. Abshire, Paula Polk, Jone Garai, Jovanny Zabaleta, Constantinos M. Mikelis, George Mattheolabakis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a63862fee7a94aa29623e74a3b9c3709
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spelling	oai:doaj.org-article:a63862fee7a94aa29623e74a3b9c37092021-12-02T11:45:00ZAdvanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance10.1038/s41598-021-85930-y2045-2322https://doaj.org/article/a63862fee7a94aa29623e74a3b9c37092021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85930-yhttps://doaj.org/toc/2045-2322Abstract This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.A K M Nawshad HossianFatema Tuz ZahraSagun PoudelCamille F. AbshirePaula PolkJone GaraiJovanny ZabaletaConstantinos M. MikelisGeorge MattheolabakisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A K M Nawshad Hossian Fatema Tuz Zahra Sagun Poudel Camille F. Abshire Paula Polk Jone Garai Jovanny Zabaleta Constantinos M. Mikelis George Mattheolabakis Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
description	Abstract This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.
format	article
author	A K M Nawshad Hossian Fatema Tuz Zahra Sagun Poudel Camille F. Abshire Paula Polk Jone Garai Jovanny Zabaleta Constantinos M. Mikelis George Mattheolabakis
author_facet	A K M Nawshad Hossian Fatema Tuz Zahra Sagun Poudel Camille F. Abshire Paula Polk Jone Garai Jovanny Zabaleta Constantinos M. Mikelis George Mattheolabakis
author_sort	A K M Nawshad Hossian
title	Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
title_short	Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
title_full	Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
title_fullStr	Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
title_full_unstemmed	Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
title_sort	advanced bioinformatic analysis and pathway prediction of nsclc cells upon cisplatin resistance
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a63862fee7a94aa29623e74a3b9c3709
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Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance

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