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A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma

MiR-21-5p is one of the most common oncogenic miRNAs that is upregulated in many solid cancers by inhibiting its target genes at the posttranscriptional level. However, the upstream regulatory mechanisms of miR-21-5p are still not well documented in cancers. Here, we identify a super-enhancer associ...

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Autores principales: Wan, Yuehan, Hoyle, Rosalie G., Xie, Nan, Wang, Wenjin, Cai, Hongshi, Zhang, Ming, Ma, Zhikun, Xiong, Gan, Xu, Xiuyun, Huang, Zhengxian, Liu, Xiqiang, Li, Jiong, Wang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085558/
https://www.ncbi.nlm.nih.gov/pubmed/33937067
http://dx.doi.org/10.3389/fonc.2021.656628
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author Wan, Yuehan
Hoyle, Rosalie G.
Xie, Nan
Wang, Wenjin
Cai, Hongshi
Zhang, Ming
Ma, Zhikun
Xiong, Gan
Xu, Xiuyun
Huang, Zhengxian
Liu, Xiqiang
Li, Jiong
Wang, Cheng
author_facet Wan, Yuehan
Hoyle, Rosalie G.
Xie, Nan
Wang, Wenjin
Cai, Hongshi
Zhang, Ming
Ma, Zhikun
Xiong, Gan
Xu, Xiuyun
Huang, Zhengxian
Liu, Xiqiang
Li, Jiong
Wang, Cheng
author_sort Wan, Yuehan
collection PubMed
description MiR-21-5p is one of the most common oncogenic miRNAs that is upregulated in many solid cancers by inhibiting its target genes at the posttranscriptional level. However, the upstream regulatory mechanisms of miR-21-5p are still not well documented in cancers. Here, we identify a super-enhancer associated with the MIR21 gene (MIR21-SE) by analyzing the MIR21 genomic regulatory landscape in head and neck squamous cell carcinoma (HNSCC). We show that the MIR21-SE regulates miR-21-5p expression in different HNSCC cell lines and disruption of MIR21-SE inhibits miR-21-5p expression. We also identified that a key transcription factor, FOSL1 directly controls miR-21-5p expression by interacting with the MIR21-SE in HNSCC. Moreover, functional studies indicate that restoration of miR-21-5p partially abrogates FOSL1 depletion-mediated inhibition of cell proliferation and invasion. Clinical studies confirmed that miR-21-5p expression is positively correlated with FOSL1 expression. These findings suggest that FOSL1-SE drives miR-21-5p expression to promote malignant progression of HNSCC
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spelling pubmed-80855582021-05-01 A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma Wan, Yuehan Hoyle, Rosalie G. Xie, Nan Wang, Wenjin Cai, Hongshi Zhang, Ming Ma, Zhikun Xiong, Gan Xu, Xiuyun Huang, Zhengxian Liu, Xiqiang Li, Jiong Wang, Cheng Front Oncol Oncology MiR-21-5p is one of the most common oncogenic miRNAs that is upregulated in many solid cancers by inhibiting its target genes at the posttranscriptional level. However, the upstream regulatory mechanisms of miR-21-5p are still not well documented in cancers. Here, we identify a super-enhancer associated with the MIR21 gene (MIR21-SE) by analyzing the MIR21 genomic regulatory landscape in head and neck squamous cell carcinoma (HNSCC). We show that the MIR21-SE regulates miR-21-5p expression in different HNSCC cell lines and disruption of MIR21-SE inhibits miR-21-5p expression. We also identified that a key transcription factor, FOSL1 directly controls miR-21-5p expression by interacting with the MIR21-SE in HNSCC. Moreover, functional studies indicate that restoration of miR-21-5p partially abrogates FOSL1 depletion-mediated inhibition of cell proliferation and invasion. Clinical studies confirmed that miR-21-5p expression is positively correlated with FOSL1 expression. These findings suggest that FOSL1-SE drives miR-21-5p expression to promote malignant progression of HNSCC Frontiers Media S.A. 2021-04-16 /pmc/articles/PMC8085558/ /pubmed/33937067 http://dx.doi.org/10.3389/fonc.2021.656628 Text en Copyright © 2021 Wan, Hoyle, Xie, Wang, Cai, Zhang, Ma, Xiong, Xu, Huang, Liu, Li and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wan, Yuehan
Hoyle, Rosalie G.
Xie, Nan
Wang, Wenjin
Cai, Hongshi
Zhang, Ming
Ma, Zhikun
Xiong, Gan
Xu, Xiuyun
Huang, Zhengxian
Liu, Xiqiang
Li, Jiong
Wang, Cheng
A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma
title A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma
title_full A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma
title_fullStr A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma
title_short A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma
title_sort super-enhancer driven by fosl1 controls mir-21-5p expression in head and neck squamous cell carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085558/
https://www.ncbi.nlm.nih.gov/pubmed/33937067
http://dx.doi.org/10.3389/fonc.2021.656628
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