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LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus
BACKGROUND: The lncRNA LINC00460 plays crucial roles in several epithelial cancers, although its mechanisms of action differ greatly in different cellular contexts. In this study, we aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700841/ https://www.ncbi.nlm.nih.gov/pubmed/31429766 http://dx.doi.org/10.1186/s13046-019-1364-z |
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author | Jiang, Yingying Cao, Wei Wu, Kun Qin, Xing Wang, Xiaoning Li, Yan Yu, Binbin Zhang, Zhen Wang, Xu Yan, Ming Xu, Qin Zhang, Jianjun Chen, Wantao |
author_facet | Jiang, Yingying Cao, Wei Wu, Kun Qin, Xing Wang, Xiaoning Li, Yan Yu, Binbin Zhang, Zhen Wang, Xu Yan, Ming Xu, Qin Zhang, Jianjun Chen, Wantao |
author_sort | Jiang, Yingying |
collection | PubMed |
description | BACKGROUND: The lncRNA LINC00460 plays crucial roles in several epithelial cancers, although its mechanisms of action differ greatly in different cellular contexts. In this study, we aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 affects the development and progression of head and neck squamous cell carcinoma (HNSCC). METHODS: The biological functions of LINC00460 were assessed in several epithelial cancer cell lines. The subcellular localization of LINC00460 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization. RNA pull-down assays, LS-MS/MS analysis, and RNA and chromatin immunoprecipitation assays were performed to identify the molecular mechanism by which LINC00460 promotes HNSCC progression. The clinical pathological features of LINC00460 and PRDX1 were evaluated in HNSCC tissues and paired adjacent normal tissues. RESULTS: LINC00460 enhanced HNSCC cell proliferation and metastasis in vitro and in vivo and induced epithelial–mesenchymal transition (EMT). LINC00460 primarily localized within the cytoplasm of HNSCC cells, physically interacted with PRDX1 and facilitated PRDX1 entry into the nucleus. PRDX1 promoted the transcription of LINC00460, forming a positive feedback loop. In addition, PRDX1 also promoted the transcription of EMT-related genes (such as ZEB1, ZEB2 and VIM) through enrichment on gene promoters in the nucleus. LINC00460 effectively induced HNSCC cell EMT in a PRDX1-dependent manner, and PRDX1 mainly mediated the EMT-promoting effect of LINC00460. High levels of LINC00460 and PRDX1 expression were positively associated with lymph metastasis, pathological differentiation and tumor size in HNSCC patients. CONCLUSIONS: LINC00460 promoted EMT in HNSCC cells by facilitating PRDX1 entry into the nucleus. LINC00460 and PRDX1 are promising candidate prognostic predictors and potential targets for cancer therapy for HNSCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1364-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6700841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67008412019-08-26 LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus Jiang, Yingying Cao, Wei Wu, Kun Qin, Xing Wang, Xiaoning Li, Yan Yu, Binbin Zhang, Zhen Wang, Xu Yan, Ming Xu, Qin Zhang, Jianjun Chen, Wantao J Exp Clin Cancer Res Research BACKGROUND: The lncRNA LINC00460 plays crucial roles in several epithelial cancers, although its mechanisms of action differ greatly in different cellular contexts. In this study, we aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 affects the development and progression of head and neck squamous cell carcinoma (HNSCC). METHODS: The biological functions of LINC00460 were assessed in several epithelial cancer cell lines. The subcellular localization of LINC00460 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization. RNA pull-down assays, LS-MS/MS analysis, and RNA and chromatin immunoprecipitation assays were performed to identify the molecular mechanism by which LINC00460 promotes HNSCC progression. The clinical pathological features of LINC00460 and PRDX1 were evaluated in HNSCC tissues and paired adjacent normal tissues. RESULTS: LINC00460 enhanced HNSCC cell proliferation and metastasis in vitro and in vivo and induced epithelial–mesenchymal transition (EMT). LINC00460 primarily localized within the cytoplasm of HNSCC cells, physically interacted with PRDX1 and facilitated PRDX1 entry into the nucleus. PRDX1 promoted the transcription of LINC00460, forming a positive feedback loop. In addition, PRDX1 also promoted the transcription of EMT-related genes (such as ZEB1, ZEB2 and VIM) through enrichment on gene promoters in the nucleus. LINC00460 effectively induced HNSCC cell EMT in a PRDX1-dependent manner, and PRDX1 mainly mediated the EMT-promoting effect of LINC00460. High levels of LINC00460 and PRDX1 expression were positively associated with lymph metastasis, pathological differentiation and tumor size in HNSCC patients. CONCLUSIONS: LINC00460 promoted EMT in HNSCC cells by facilitating PRDX1 entry into the nucleus. LINC00460 and PRDX1 are promising candidate prognostic predictors and potential targets for cancer therapy for HNSCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1364-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-20 /pmc/articles/PMC6700841/ /pubmed/31429766 http://dx.doi.org/10.1186/s13046-019-1364-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Jiang, Yingying Cao, Wei Wu, Kun Qin, Xing Wang, Xiaoning Li, Yan Yu, Binbin Zhang, Zhen Wang, Xu Yan, Ming Xu, Qin Zhang, Jianjun Chen, Wantao LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
title | LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
title_full | LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
title_fullStr | LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
title_full_unstemmed | LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
title_short | LncRNA LINC00460 promotes EMT in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
title_sort | lncrna linc00460 promotes emt in head and neck squamous cell carcinoma by facilitating peroxiredoxin-1 into the nucleus |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700841/ https://www.ncbi.nlm.nih.gov/pubmed/31429766 http://dx.doi.org/10.1186/s13046-019-1364-z |
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