Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug

Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p r...

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Autores principales:	Xinxin Liang, Ziyan Yan, Ping Wang, Yuhao Liu, Xingkun Ao, Zheng Liu, Duo Wang, Xiaochang Liu, Maoxiang Zhu, Shanshan Gao, Dafei Xie, Pingkun Zhou, Yongqing Gu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	miR-541-5p EMT slug MZF1 radiation-induced pulmonary fibrosis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/bc3b2de16424464e9cb469b3b5cf972e
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spelling	oai:doaj.org-article:bc3b2de16424464e9cb469b3b5cf972e2021-11-11T16:48:24ZIrradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug10.3390/ijms2221113091422-00671661-6596https://doaj.org/article/bc3b2de16424464e9cb469b3b5cf972e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11309https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (<i>MZF1</i>) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor <i>MZF1</i> upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the <i>Slug</i> on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting <i>Slug</i>. Thus, irradiation activates <i>MZF1</i> to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting <i>Slug</i>. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.Xinxin LiangZiyan YanPing WangYuhao LiuXingkun AoZheng LiuDuo WangXiaochang LiuMaoxiang ZhuShanshan GaoDafei XiePingkun ZhouYongqing GuMDPI AGarticlemiR-541-5pEMTslugMZF1radiation-induced pulmonary fibrosisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11309, p 11309 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-541-5p EMT slug MZF1 radiation-induced pulmonary fibrosis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	miR-541-5p EMT slug MZF1 radiation-induced pulmonary fibrosis Biology (General) QH301-705.5 Chemistry QD1-999 Xinxin Liang Ziyan Yan Ping Wang Yuhao Liu Xingkun Ao Zheng Liu Duo Wang Xiaochang Liu Maoxiang Zhu Shanshan Gao Dafei Xie Pingkun Zhou Yongqing Gu Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
description	Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (<i>MZF1</i>) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor <i>MZF1</i> upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the <i>Slug</i> on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting <i>Slug</i>. Thus, irradiation activates <i>MZF1</i> to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting <i>Slug</i>. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.
format	article
author	Xinxin Liang Ziyan Yan Ping Wang Yuhao Liu Xingkun Ao Zheng Liu Duo Wang Xiaochang Liu Maoxiang Zhu Shanshan Gao Dafei Xie Pingkun Zhou Yongqing Gu
author_facet	Xinxin Liang Ziyan Yan Ping Wang Yuhao Liu Xingkun Ao Zheng Liu Duo Wang Xiaochang Liu Maoxiang Zhu Shanshan Gao Dafei Xie Pingkun Zhou Yongqing Gu
author_sort	Xinxin Liang
title	Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
title_short	Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
title_full	Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
title_fullStr	Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
title_full_unstemmed	Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
title_sort	irradiation activates mzf1 to inhibit mir-541-5p expression and promote epithelial-mesenchymal transition (emt) in radiation-induced pulmonary fibrosis (ripf) by upregulating slug
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bc3b2de16424464e9cb469b3b5cf972e
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Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug

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