FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling

Abstract Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transfor...

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Auteurs principaux:	Xiaoshan Su, Junjie Chen, Xiaoping Lin, Xiaoyang Chen, Zhixing Zhu, Weijing Wu, Hai Lin, Jianming Wang, Xiangjia Ye, Yiming Zeng
Format:	article
Langue:	EN
Publié:	BMC 2021
Sujets:	FERMT3 EMT COPD Wnt/β-catenin Diseases of the respiratory system RC705-779
Accès en ligne:	https://doaj.org/article/ae224e6ff6af4f55b41a3822698a99e7
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spelling	oai:doaj.org-article:ae224e6ff6af4f55b41a3822698a99e72021-11-08T11:03:46ZFERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling10.1186/s12931-021-01881-y1465-993Xhttps://doaj.org/article/ae224e6ff6af4f55b41a3822698a99e72021-11-01T00:00:00Zhttps://doi.org/10.1186/s12931-021-01881-yhttps://doaj.org/toc/1465-993XAbstract Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.Xiaoshan SuJunjie ChenXiaoping LinXiaoyang ChenZhixing ZhuWeijing WuHai LinJianming WangXiangjia YeYiming ZengBMCarticleFERMT3EMTCOPDWnt/β-cateninDiseases of the respiratory systemRC705-779ENRespiratory Research, Vol 22, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FERMT3 EMT COPD Wnt/β-catenin Diseases of the respiratory system RC705-779
spellingShingle	FERMT3 EMT COPD Wnt/β-catenin Diseases of the respiratory system RC705-779 Xiaoshan Su Junjie Chen Xiaoping Lin Xiaoyang Chen Zhixing Zhu Weijing Wu Hai Lin Jianming Wang Xiangjia Ye Yiming Zeng FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
description	Abstract Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.
format	article
author	Xiaoshan Su Junjie Chen Xiaoping Lin Xiaoyang Chen Zhixing Zhu Weijing Wu Hai Lin Jianming Wang Xiangjia Ye Yiming Zeng
author_facet	Xiaoshan Su Junjie Chen Xiaoping Lin Xiaoyang Chen Zhixing Zhu Weijing Wu Hai Lin Jianming Wang Xiangjia Ye Yiming Zeng
author_sort	Xiaoshan Su
title	FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
title_short	FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
title_full	FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
title_fullStr	FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
title_full_unstemmed	FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
title_sort	fermt3 mediates cigarette smoke-induced epithelial–mesenchymal transition through wnt/β-catenin signaling
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ae224e6ff6af4f55b41a3822698a99e7
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_version_	1718442458206961664

FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling

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