Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice

Abstract Background Chronic obstructive pulmonary disease (COPD) remains a prevalent chronic airway inflammatory disease. Circular RNAs (circRNAs) are associated with inflammation regulation; therefore, we examined distinct effects of circRNA FOXO3 (circFOXO3) against pneumonic inflammatory processe...

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Autores principales:	Lei Zhou, Bo Wu, Jun Yang, Bing Wang, Jing Pan, Donghui Xu, Chunling Du
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	COPD Circular RNA FOXO3 miR-214-3p NF-κB Lung inflammation Diseases of the respiratory system RC705-779
Acceso en línea:	https://doaj.org/article/2c98aa3e4b524375b1dd485b64bf8ec7
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spelling	oai:doaj.org-article:2c98aa3e4b524375b1dd485b64bf8ec72021-11-21T12:31:57ZKnockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice10.1186/s12931-021-01883-w1465-993Xhttps://doaj.org/article/2c98aa3e4b524375b1dd485b64bf8ec72021-11-01T00:00:00Zhttps://doi.org/10.1186/s12931-021-01883-whttps://doaj.org/toc/1465-993XAbstract Background Chronic obstructive pulmonary disease (COPD) remains a prevalent chronic airway inflammatory disease. Circular RNAs (circRNAs) are associated with inflammation regulation; therefore, we examined distinct effects of circRNA FOXO3 (circFOXO3) against pneumonic inflammatory processes in COPD. Methods We first quantified and localized circFOXO3 in mouse lung epithelial cell line MLE12 by quantitative reverse-transcription PCR and in situ hybridization. Next, circFOXO3 was suppressed by therapeutic administration of circFOXO3 knockdown lentivirus in mice exposed to air or cigarette smoke (CS) for 12 weeks, and several hallmarks of COPD were evaluated. Results We noticed that circFOXO3 is upregulated in CS-exposed lungs and cigarette smoke extract (CSE)-treated murine alveolar epithelial cells. Knockdown of circFOXO3 attenuated the release of CXCL1 and IL-6 as well as inflammatory processes in the lungs of CS-exposed mice. In addition, we identified miR-214-3p as a circFOXO3-targeted microRNA. MiR-214-3p overexpression exerted protective effects against pneumonic inflammation after CS exposure. Silencing of circFOXO3 downregulated IKK-β mRNA (miR-214-3p’s target), resulting in the dysfunction of the NF-κB signaling pathway and attenuation of CSE-induced inflammatory-cytokine expression. Conclusions Collectively, these findings reveal a crucial function of circFOXO3 in the pathological remodeling related to CS-induced inflammatory processes. Hence, circFOXO3 might be a good target for the treatment of inflammatory disorders similar to CS-induced lung inflammation.Lei ZhouBo WuJun YangBing WangJing PanDonghui XuChunling DuBMCarticleCOPDCircular RNA FOXO3miR-214-3pNF-κBLung inflammationDiseases of the respiratory systemRC705-779ENRespiratory Research, Vol 22, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COPD Circular RNA FOXO3 miR-214-3p NF-κB Lung inflammation Diseases of the respiratory system RC705-779
spellingShingle	COPD Circular RNA FOXO3 miR-214-3p NF-κB Lung inflammation Diseases of the respiratory system RC705-779 Lei Zhou Bo Wu Jun Yang Bing Wang Jing Pan Donghui Xu Chunling Du Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
description	Abstract Background Chronic obstructive pulmonary disease (COPD) remains a prevalent chronic airway inflammatory disease. Circular RNAs (circRNAs) are associated with inflammation regulation; therefore, we examined distinct effects of circRNA FOXO3 (circFOXO3) against pneumonic inflammatory processes in COPD. Methods We first quantified and localized circFOXO3 in mouse lung epithelial cell line MLE12 by quantitative reverse-transcription PCR and in situ hybridization. Next, circFOXO3 was suppressed by therapeutic administration of circFOXO3 knockdown lentivirus in mice exposed to air or cigarette smoke (CS) for 12 weeks, and several hallmarks of COPD were evaluated. Results We noticed that circFOXO3 is upregulated in CS-exposed lungs and cigarette smoke extract (CSE)-treated murine alveolar epithelial cells. Knockdown of circFOXO3 attenuated the release of CXCL1 and IL-6 as well as inflammatory processes in the lungs of CS-exposed mice. In addition, we identified miR-214-3p as a circFOXO3-targeted microRNA. MiR-214-3p overexpression exerted protective effects against pneumonic inflammation after CS exposure. Silencing of circFOXO3 downregulated IKK-β mRNA (miR-214-3p’s target), resulting in the dysfunction of the NF-κB signaling pathway and attenuation of CSE-induced inflammatory-cytokine expression. Conclusions Collectively, these findings reveal a crucial function of circFOXO3 in the pathological remodeling related to CS-induced inflammatory processes. Hence, circFOXO3 might be a good target for the treatment of inflammatory disorders similar to CS-induced lung inflammation.
format	article
author	Lei Zhou Bo Wu Jun Yang Bing Wang Jing Pan Donghui Xu Chunling Du
author_facet	Lei Zhou Bo Wu Jun Yang Bing Wang Jing Pan Donghui Xu Chunling Du
author_sort	Lei Zhou
title	Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
title_short	Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
title_full	Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
title_fullStr	Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
title_full_unstemmed	Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
title_sort	knockdown of circfoxo3 ameliorates cigarette smoke-induced lung injury in mice
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2c98aa3e4b524375b1dd485b64bf8ec7
work_keys_str_mv	AT leizhou knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice AT bowu knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice AT junyang knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice AT bingwang knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice AT jingpan knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice AT donghuixu knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice AT chunlingdu knockdownofcircfoxo3amelioratescigarettesmokeinducedlunginjuryinmice
_version_	1718418933381332992

Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice

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