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MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway
BACKGROUND: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711887/ https://www.ncbi.nlm.nih.gov/pubmed/31383552 http://dx.doi.org/10.1016/j.ebiom.2019.07.050 |
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author | Wang, Wei-Wei Zhao, Zhi-Hua Wang, Li Li, Pan Chen, Kui-Sheng Zhang, Jian-Ying Li, Wen-Cai Jiang, Guo-Zhong Li, Xiang-Nan |
author_facet | Wang, Wei-Wei Zhao, Zhi-Hua Wang, Li Li, Pan Chen, Kui-Sheng Zhang, Jian-Ying Li, Wen-Cai Jiang, Guo-Zhong Li, Xiang-Nan |
author_sort | Wang, Wei-Wei |
collection | PubMed |
description | BACKGROUND: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. METHODS: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. FINDINGS: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. INTERPRETATION: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC. |
format | Online Article Text |
id | pubmed-6711887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-67118872019-08-29 MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway Wang, Wei-Wei Zhao, Zhi-Hua Wang, Li Li, Pan Chen, Kui-Sheng Zhang, Jian-Ying Li, Wen-Cai Jiang, Guo-Zhong Li, Xiang-Nan EBioMedicine Research paper BACKGROUND: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. METHODS: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. FINDINGS: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. INTERPRETATION: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC. Elsevier 2019-08-02 /pmc/articles/PMC6711887/ /pubmed/31383552 http://dx.doi.org/10.1016/j.ebiom.2019.07.050 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Wang, Wei-Wei Zhao, Zhi-Hua Wang, Li Li, Pan Chen, Kui-Sheng Zhang, Jian-Ying Li, Wen-Cai Jiang, Guo-Zhong Li, Xiang-Nan MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway |
title | MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway |
title_full | MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway |
title_fullStr | MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway |
title_full_unstemmed | MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway |
title_short | MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway |
title_sort | microrna-134 prevents the progression of esophageal squamous cell carcinoma via the plxna1-mediated mapk signalling pathway |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711887/ https://www.ncbi.nlm.nih.gov/pubmed/31383552 http://dx.doi.org/10.1016/j.ebiom.2019.07.050 |
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