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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

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: Liang, Xinxin, Yan, Ziyan, Wang, Ping, Liu, Yuhao, Ao, Xingkun, Liu, Zheng, Wang, Duo, Liu, Xiaochang, Zhu, Maoxiang, Gao, Shanshan, Xie, Dafei, Zhou, Pingkun, Gu, Yongqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582843/
https://www.ncbi.nlm.nih.gov/pubmed/34768749
http://dx.doi.org/10.3390/ijms222111309
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author Liang, Xinxin
Yan, Ziyan
Wang, Ping
Liu, Yuhao
Ao, Xingkun
Liu, Zheng
Wang, Duo
Liu, Xiaochang
Zhu, Maoxiang
Gao, Shanshan
Xie, Dafei
Zhou, Pingkun
Gu, Yongqing
author_facet Liang, Xinxin
Yan, Ziyan
Wang, Ping
Liu, Yuhao
Ao, Xingkun
Liu, Zheng
Wang, Duo
Liu, Xiaochang
Zhu, Maoxiang
Gao, Shanshan
Xie, Dafei
Zhou, Pingkun
Gu, Yongqing
author_sort Liang, Xinxin
collection PubMed
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 (MZF1) 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 MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.
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spelling pubmed-85828432021-11-12 Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug Liang, Xinxin Yan, Ziyan Wang, Ping Liu, Yuhao Ao, Xingkun Liu, Zheng Wang, Duo Liu, Xiaochang Zhu, Maoxiang Gao, Shanshan Xie, Dafei Zhou, Pingkun Gu, Yongqing Int J Mol Sci Article 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 (MZF1) 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 MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets. MDPI 2021-10-20 /pmc/articles/PMC8582843/ /pubmed/34768749 http://dx.doi.org/10.3390/ijms222111309 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liang, Xinxin
Yan, Ziyan
Wang, Ping
Liu, Yuhao
Ao, Xingkun
Liu, Zheng
Wang, Duo
Liu, Xiaochang
Zhu, Maoxiang
Gao, Shanshan
Xie, Dafei
Zhou, Pingkun
Gu, Yongqing
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 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_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_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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582843/
https://www.ncbi.nlm.nih.gov/pubmed/34768749
http://dx.doi.org/10.3390/ijms222111309
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