Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer

Background: Circular RNAs (circRNAs) are non-coding RNAs with a circular structure that have recently emerged as important regulators of tumorogenesis. Recently, several circRNAS, including circ-10720 have been related to epithelial-mesenchymal transition (EMT) process. In the present study, we have...

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Autores: Martín, Jara, Castellano, Joan Josep, Marrades Sicart, Ramon Ma., Canals, Jordi, Viñolas Segarra, Núria, Díaz Sánchez, Tania, Molins López-Rodó, Laureano, Martinez, Daniel, Han, Bing, Moisés, Jorge, He, Yangyi, Monzó Planella, Mariano, Navarro Ponz, Alfons
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184005
Acceso en línea:https://hdl.handle.net/2445/184005
Access Level:acceso abierto
Palabra clave:Càncer de pulmó
RNA
Lung cancer
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spelling Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancerMartín, JaraCastellano, Joan JosepMarrades Sicart, Ramon Ma.Canals, JordiViñolas Segarra, NúriaDíaz Sánchez, TaniaMolins López-Rodó, LaureanoMartinez, DanielHan, BingMoisés, JorgeHe, YangyiMonzó Planella, MarianoNavarro Ponz, AlfonsCàncer de pulmóRNALung cancerRNABackground: Circular RNAs (circRNAs) are non-coding RNAs with a circular structure that have recently emerged as important regulators of tumorogenesis. Recently, several circRNAS, including circ-10720 have been related to epithelial-mesenchymal transition (EMT) process. In the present study, we have analyzed the role of circ-10720 in non-small-cell lung cancer (NSCLC) and studied its prognostic relevance in resected stage I-IIIa NSCLC patients. Methods: Circ-10720 expression was analyzed using a custom TaqMan assay in four NSCLC cell lines (HCC44, A549, H23 and H1299) and in the normal immortalized lung cell line BEAS2B. Silencing of circ10720 was performed using two custom siRNAs which were transfected using lipofectamine 2000. Protein levels were evaluated by Western blot and immunofluorescence. Wound healing and invasion assays were performed to evaluate the impact the circRNA on cell motility. Apoptosis was analyzed by evaluation of Caspase 3-7 activity and proliferation by MTS assay. Moreover, the expression levels of the circRNA were studied in 119 resected NSCLC patients. The expression in tumor tissue was correlated with the main clinicopathological characteristics and with time to relapse (TTR). Results: Circ-10720 was overexpressed in HCC44 and A549 and underexpressed in H23 and H1299 NSCLC cell lines in comparison to BEAS2B normal immortalized lung cell line. CircRNA knockdown in the two circ-10720 overexpressing cell lines was associated with a decrease of Vimentin (VIM) and an increase of E-cadherin (CDH1) protein levels, loss of mesenchymal phenotype, and a significant reduction of migration and invasion capacity. After silencing circ-10720, the apoptosis rate increased and the proliferation was significantly reduced. Furthermore, circ-10720 was upregulated in tumor vs. normal tissue from 119 resected NSCLC patients. In the group of patients not receiving adjuvant treatment, those with high levels of circ-10720 had a shorter TTR than those with low levels and emerged as an independent prognostic value in the multivariate analysis. In tumor tissue, circ-10720 levels positively correlated with the EMT gene Twist1 levels. Conclusions: Circ-10720 regulates EMT, apoptosis and proliferation and acts as a biomarker of relapse in NSCLC.AME Publishing Company2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/184005Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.21037/tlcr-20-920Translational Lung Cancer Research, 2021, vol. 10, num. 4, p. 1804-1818https://doi.org/10.21037/tlcr-20-920cc-by-nc-nd (c) AME Publishing Company, 2021https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1840052026-05-27T06:46:51Z
dc.title.none.fl_str_mv Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
title Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
spellingShingle Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
Martín, Jara
Càncer de pulmó
RNA
Lung cancer
RNA
title_short Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
title_full Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
title_fullStr Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
title_full_unstemmed Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
title_sort Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer
dc.creator.none.fl_str_mv Martín, Jara
Castellano, Joan Josep
Marrades Sicart, Ramon Ma.
Canals, Jordi
Viñolas Segarra, Núria
Díaz Sánchez, Tania
Molins López-Rodó, Laureano
Martinez, Daniel
Han, Bing
Moisés, Jorge
He, Yangyi
Monzó Planella, Mariano
Navarro Ponz, Alfons
author Martín, Jara
author_facet Martín, Jara
Castellano, Joan Josep
Marrades Sicart, Ramon Ma.
Canals, Jordi
Viñolas Segarra, Núria
Díaz Sánchez, Tania
Molins López-Rodó, Laureano
Martinez, Daniel
Han, Bing
Moisés, Jorge
He, Yangyi
Monzó Planella, Mariano
Navarro Ponz, Alfons
author_role author
author2 Castellano, Joan Josep
Marrades Sicart, Ramon Ma.
Canals, Jordi
Viñolas Segarra, Núria
Díaz Sánchez, Tania
Molins López-Rodó, Laureano
Martinez, Daniel
Han, Bing
Moisés, Jorge
He, Yangyi
Monzó Planella, Mariano
Navarro Ponz, Alfons
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de pulmó
RNA
Lung cancer
RNA
topic Càncer de pulmó
RNA
Lung cancer
RNA
description Background: Circular RNAs (circRNAs) are non-coding RNAs with a circular structure that have recently emerged as important regulators of tumorogenesis. Recently, several circRNAS, including circ-10720 have been related to epithelial-mesenchymal transition (EMT) process. In the present study, we have analyzed the role of circ-10720 in non-small-cell lung cancer (NSCLC) and studied its prognostic relevance in resected stage I-IIIa NSCLC patients. Methods: Circ-10720 expression was analyzed using a custom TaqMan assay in four NSCLC cell lines (HCC44, A549, H23 and H1299) and in the normal immortalized lung cell line BEAS2B. Silencing of circ10720 was performed using two custom siRNAs which were transfected using lipofectamine 2000. Protein levels were evaluated by Western blot and immunofluorescence. Wound healing and invasion assays were performed to evaluate the impact the circRNA on cell motility. Apoptosis was analyzed by evaluation of Caspase 3-7 activity and proliferation by MTS assay. Moreover, the expression levels of the circRNA were studied in 119 resected NSCLC patients. The expression in tumor tissue was correlated with the main clinicopathological characteristics and with time to relapse (TTR). Results: Circ-10720 was overexpressed in HCC44 and A549 and underexpressed in H23 and H1299 NSCLC cell lines in comparison to BEAS2B normal immortalized lung cell line. CircRNA knockdown in the two circ-10720 overexpressing cell lines was associated with a decrease of Vimentin (VIM) and an increase of E-cadherin (CDH1) protein levels, loss of mesenchymal phenotype, and a significant reduction of migration and invasion capacity. After silencing circ-10720, the apoptosis rate increased and the proliferation was significantly reduced. Furthermore, circ-10720 was upregulated in tumor vs. normal tissue from 119 resected NSCLC patients. In the group of patients not receiving adjuvant treatment, those with high levels of circ-10720 had a shorter TTR than those with low levels and emerged as an independent prognostic value in the multivariate analysis. In tumor tissue, circ-10720 levels positively correlated with the EMT gene Twist1 levels. Conclusions: Circ-10720 regulates EMT, apoptosis and proliferation and acts as a biomarker of relapse in NSCLC.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/184005
url https://hdl.handle.net/2445/184005
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.21037/tlcr-20-920
Translational Lung Cancer Research, 2021, vol. 10, num. 4, p. 1804-1818
https://doi.org/10.21037/tlcr-20-920
dc.rights.none.fl_str_mv cc-by-nc-nd (c) AME Publishing Company, 2021
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) AME Publishing Company, 2021
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv AME Publishing Company
publisher.none.fl_str_mv AME Publishing Company
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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