Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells

Abstract Lung cancer is the leading cause of cancer deaths worldwide, with smoking as its primary predisposing factor. Although carcinogens in cigarettes are known to cause oncogenic DNA alterations, analyses of patient cohorts revealed heterogeneous genetic aberrations with no clear driver mutation...

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Autores principales:	Carmela Rieline V. Cruz, Jose Lorenzo M. Ferrer, Reynaldo L. Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c456273dd554cc4b283e35fc9ed7419
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spelling	oai:doaj.org-article:5c456273dd554cc4b283e35fc9ed74192021-12-02T18:50:48ZConcomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells10.1038/s41598-021-97869-12045-2322https://doaj.org/article/5c456273dd554cc4b283e35fc9ed74192021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97869-1https://doaj.org/toc/2045-2322Abstract Lung cancer is the leading cause of cancer deaths worldwide, with smoking as its primary predisposing factor. Although carcinogens in cigarettes are known to cause oncogenic DNA alterations, analyses of patient cohorts revealed heterogeneous genetic aberrations with no clear driver mutations. The contribution of noncoding RNAs (ncRNAs) in the pathogenesis of lung cancer has since been demonstrated. Their dysregulation has been linked to cancer initiation and progression. A novel long noncoding RNA (lncRNA) called smoke and cancer-associated lncRNA 1 (SCAL1) was recently found upregulated in smoke-exposed adenocarcinomic alveolar epithelial cells. The present study characterized the phenotypic consequences of SCAL1 overexpression and knockdown using A549 cells as model system, with or without prior exposure to cigarette smoke extract (CSE). Increase in SCAL1 levels either by CSE treatment or SCAL1 overexpression led to increased cell migration, extensive cytoskeletal remodeling, and resistance to apoptosis. Further, SCAL1 levels were negatively correlated with intracellular levels of reactive oxygen species (ROS). In contrast, SCAL1 knockdown showed converse results for these assays. These results confirm the oncogenic function of SCAL1 and its role as a CSE-activated lncRNA that mediates ROS detoxification in A549 cells, thereby allowing them to develop resistance to and survive smoke-induced toxicity.Carmela Rieline V. CruzJose Lorenzo M. FerrerReynaldo L. GarciaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carmela Rieline V. Cruz Jose Lorenzo M. Ferrer Reynaldo L. Garcia Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells
description	Abstract Lung cancer is the leading cause of cancer deaths worldwide, with smoking as its primary predisposing factor. Although carcinogens in cigarettes are known to cause oncogenic DNA alterations, analyses of patient cohorts revealed heterogeneous genetic aberrations with no clear driver mutations. The contribution of noncoding RNAs (ncRNAs) in the pathogenesis of lung cancer has since been demonstrated. Their dysregulation has been linked to cancer initiation and progression. A novel long noncoding RNA (lncRNA) called smoke and cancer-associated lncRNA 1 (SCAL1) was recently found upregulated in smoke-exposed adenocarcinomic alveolar epithelial cells. The present study characterized the phenotypic consequences of SCAL1 overexpression and knockdown using A549 cells as model system, with or without prior exposure to cigarette smoke extract (CSE). Increase in SCAL1 levels either by CSE treatment or SCAL1 overexpression led to increased cell migration, extensive cytoskeletal remodeling, and resistance to apoptosis. Further, SCAL1 levels were negatively correlated with intracellular levels of reactive oxygen species (ROS). In contrast, SCAL1 knockdown showed converse results for these assays. These results confirm the oncogenic function of SCAL1 and its role as a CSE-activated lncRNA that mediates ROS detoxification in A549 cells, thereby allowing them to develop resistance to and survive smoke-induced toxicity.
format	article
author	Carmela Rieline V. Cruz Jose Lorenzo M. Ferrer Reynaldo L. Garcia
author_facet	Carmela Rieline V. Cruz Jose Lorenzo M. Ferrer Reynaldo L. Garcia
author_sort	Carmela Rieline V. Cruz
title	Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells
title_short	Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells
title_full	Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells
title_fullStr	Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells
title_full_unstemmed	Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells
title_sort	concomitant and decoupled effects of cigarette smoke and scal1 upregulation on oncogenic phenotypes and ros detoxification in lung adenocarcinoma cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5c456273dd554cc4b283e35fc9ed7419
work_keys_str_mv	AT carmelarielinevcruz concomitantanddecoupledeffectsofcigarettesmokeandscal1upregulationononcogenicphenotypesandrosdetoxificationinlungadenocarcinomacells AT joselorenzomferrer concomitantanddecoupledeffectsofcigarettesmokeandscal1upregulationononcogenicphenotypesandrosdetoxificationinlungadenocarcinomacells AT reynaldolgarcia concomitantanddecoupledeffectsofcigarettesmokeandscal1upregulationononcogenicphenotypesandrosdetoxificationinlungadenocarcinomacells
_version_	1718377505180614656

Concomitant and decoupled effects of cigarette smoke and SCAL1 upregulation on oncogenic phenotypes and ROS detoxification in lung adenocarcinoma cells

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