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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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 |
format | Online Article Text |
id | pubmed-8085558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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