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The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma

Oesophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy. Although many molecular alterations have been observed in ESCC, the mechanisms underlying the development and progression of this disease remain unclear. In the present study, miR-1224-5p was identified to be downregul...

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Autores principales: Shi, Zhi-Zhou, Wang, Wen-Jun, Chen, Yun-Xia, Fan, Ze-Wen, Xie, Xiu-Feng, Yang, Li-Yan, Chang, Chen, Cai, Yan, Hao, Jia-Jie, Wang, Ming-Rong, Bai, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393493/
https://www.ncbi.nlm.nih.gov/pubmed/32732965
http://dx.doi.org/10.1038/s41419-020-02801-6
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author Shi, Zhi-Zhou
Wang, Wen-Jun
Chen, Yun-Xia
Fan, Ze-Wen
Xie, Xiu-Feng
Yang, Li-Yan
Chang, Chen
Cai, Yan
Hao, Jia-Jie
Wang, Ming-Rong
Bai, Jie
author_facet Shi, Zhi-Zhou
Wang, Wen-Jun
Chen, Yun-Xia
Fan, Ze-Wen
Xie, Xiu-Feng
Yang, Li-Yan
Chang, Chen
Cai, Yan
Hao, Jia-Jie
Wang, Ming-Rong
Bai, Jie
author_sort Shi, Zhi-Zhou
collection PubMed
description Oesophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy. Although many molecular alterations have been observed in ESCC, the mechanisms underlying the development and progression of this disease remain unclear. In the present study, miR-1224-5p was identified to be downregulated in ESCC tissues compared to normal tissues, and its low expression was correlated with shorter survival time in patients. In vitro experiments showed that miR-1224-5p inhibited the proliferation, colony formation, migration and invasion of ESCC cells. Mechanistic investigation revealed that miR-1224-5p directly targeted TNS4 and inhibited its expression, which led to the inactivation of EGFR-EFNA1/EPHA2-VEGFA (vascular endothelial growth factor A) signalling. Experiments in vivo confirmed the suppressive effect of miR-1224-5p on oesophageal cancer cells. By immunohistochemistry analysis of ESCC specimens, we found that TNS4 expression was positively correlated with that of VEGFA, and was significantly associated with lymph node metastasis and shorter survival time in patients. Together, our data suggest that miR-1224-5p downregulation is a frequent alteration in ESCC that promotes cell proliferation, migration, invasion and tumour growth by activating the EGFR-EFNA1/EPHA2-VEGFA signalling pathway via inhibition of TNS4 expression. Decreased miR-1224-5p and elevated TNS4 are unfavourable prognostic factors for ESCC patients.
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spelling pubmed-73934932020-08-18 The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma Shi, Zhi-Zhou Wang, Wen-Jun Chen, Yun-Xia Fan, Ze-Wen Xie, Xiu-Feng Yang, Li-Yan Chang, Chen Cai, Yan Hao, Jia-Jie Wang, Ming-Rong Bai, Jie Cell Death Dis Article Oesophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy. Although many molecular alterations have been observed in ESCC, the mechanisms underlying the development and progression of this disease remain unclear. In the present study, miR-1224-5p was identified to be downregulated in ESCC tissues compared to normal tissues, and its low expression was correlated with shorter survival time in patients. In vitro experiments showed that miR-1224-5p inhibited the proliferation, colony formation, migration and invasion of ESCC cells. Mechanistic investigation revealed that miR-1224-5p directly targeted TNS4 and inhibited its expression, which led to the inactivation of EGFR-EFNA1/EPHA2-VEGFA (vascular endothelial growth factor A) signalling. Experiments in vivo confirmed the suppressive effect of miR-1224-5p on oesophageal cancer cells. By immunohistochemistry analysis of ESCC specimens, we found that TNS4 expression was positively correlated with that of VEGFA, and was significantly associated with lymph node metastasis and shorter survival time in patients. Together, our data suggest that miR-1224-5p downregulation is a frequent alteration in ESCC that promotes cell proliferation, migration, invasion and tumour growth by activating the EGFR-EFNA1/EPHA2-VEGFA signalling pathway via inhibition of TNS4 expression. Decreased miR-1224-5p and elevated TNS4 are unfavourable prognostic factors for ESCC patients. Nature Publishing Group UK 2020-07-30 /pmc/articles/PMC7393493/ /pubmed/32732965 http://dx.doi.org/10.1038/s41419-020-02801-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shi, Zhi-Zhou
Wang, Wen-Jun
Chen, Yun-Xia
Fan, Ze-Wen
Xie, Xiu-Feng
Yang, Li-Yan
Chang, Chen
Cai, Yan
Hao, Jia-Jie
Wang, Ming-Rong
Bai, Jie
The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma
title The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma
title_full The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma
title_fullStr The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma
title_full_unstemmed The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma
title_short The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma
title_sort mir-1224-5p/tns4/egfr axis inhibits tumour progression in oesophageal squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393493/
https://www.ncbi.nlm.nih.gov/pubmed/32732965
http://dx.doi.org/10.1038/s41419-020-02801-6
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