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MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth
BACKGROUND: Anoikis resistance has been demonstrated to facilitate distant metastases of cancers. MicroRNA-133b (miR-133b) is found to be down-regulated in various tumors, including esophageal squamous cell carcinoma (ESCC), and closely correlates with the malignant phenotype of ESCC. This study aim...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251163/ https://www.ncbi.nlm.nih.gov/pubmed/30479571 http://dx.doi.org/10.1186/s12935-018-0684-y |
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author | Zhu, Jin-Feng Liu, Yi Huang, He Shan, Li Han, Zhi-Gang Liu, Jun-Yuan Li, Ying-Long Dong, Xiang Zeng, Wei |
author_facet | Zhu, Jin-Feng Liu, Yi Huang, He Shan, Li Han, Zhi-Gang Liu, Jun-Yuan Li, Ying-Long Dong, Xiang Zeng, Wei |
author_sort | Zhu, Jin-Feng |
collection | PubMed |
description | BACKGROUND: Anoikis resistance has been demonstrated to facilitate distant metastases of cancers. MicroRNA-133b (miR-133b) is found to be down-regulated in various tumors, including esophageal squamous cell carcinoma (ESCC), and closely correlates with the malignant phenotype of ESCC. This study aimed to evaluate the roles of miR-133b in metastases of ESCC via regulating anoikis. METHODS: The expression of miR-133b and related molecules were detected in ESCC tissues and cells. The target relationship between miR-133b and epidermal growth factor receptor (EGFR) was verified by dual luciferase reporter assay. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Anoikis and anchorage-independent growth were assessed by anoikis assay and soft agar assay. Migration and invasion were evaluated by scratch and transwell assays. The expressions of related molecules were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. The in vivo results were determined by tumor xenografts in nude mice. RESULTS: MiR-133b level was decreased in ESCC tissues and cells, which negatively correlated with EGFR, integrin β4 (ITGB4), and phosphorylated focal adhesion kinase levels. Moreover, miR-133b down-regulated EGFR expression in ESCC cells. Overexpression of miR-133b inhibited the anoikis resistance, migration, invasion and epithelial-mesenchymal transition of ESCC cells via targeting EGFR. Finally, miR-133b overexpression suppressed tumor growth and lung metastases of ESCC in vivo. ITGB4/FAK/growth factor receptor-bound protein 2 (Grb2), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) pathways were involved in the regulatory mechanisms of miR-133b/EGFR axis in ESCC metastases in vitro and in vivo. CONCLUSIONS: The results suggested that miR-133b/EGFR axis regulated metastases of ESCC by affecting anoikis resistance via ITGB4/FAK/Grb2, AKT, and ERK pathways. |
format | Online Article Text |
id | pubmed-6251163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62511632018-11-26 MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth Zhu, Jin-Feng Liu, Yi Huang, He Shan, Li Han, Zhi-Gang Liu, Jun-Yuan Li, Ying-Long Dong, Xiang Zeng, Wei Cancer Cell Int Primary Research BACKGROUND: Anoikis resistance has been demonstrated to facilitate distant metastases of cancers. MicroRNA-133b (miR-133b) is found to be down-regulated in various tumors, including esophageal squamous cell carcinoma (ESCC), and closely correlates with the malignant phenotype of ESCC. This study aimed to evaluate the roles of miR-133b in metastases of ESCC via regulating anoikis. METHODS: The expression of miR-133b and related molecules were detected in ESCC tissues and cells. The target relationship between miR-133b and epidermal growth factor receptor (EGFR) was verified by dual luciferase reporter assay. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Anoikis and anchorage-independent growth were assessed by anoikis assay and soft agar assay. Migration and invasion were evaluated by scratch and transwell assays. The expressions of related molecules were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. The in vivo results were determined by tumor xenografts in nude mice. RESULTS: MiR-133b level was decreased in ESCC tissues and cells, which negatively correlated with EGFR, integrin β4 (ITGB4), and phosphorylated focal adhesion kinase levels. Moreover, miR-133b down-regulated EGFR expression in ESCC cells. Overexpression of miR-133b inhibited the anoikis resistance, migration, invasion and epithelial-mesenchymal transition of ESCC cells via targeting EGFR. Finally, miR-133b overexpression suppressed tumor growth and lung metastases of ESCC in vivo. ITGB4/FAK/growth factor receptor-bound protein 2 (Grb2), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) pathways were involved in the regulatory mechanisms of miR-133b/EGFR axis in ESCC metastases in vitro and in vivo. CONCLUSIONS: The results suggested that miR-133b/EGFR axis regulated metastases of ESCC by affecting anoikis resistance via ITGB4/FAK/Grb2, AKT, and ERK pathways. BioMed Central 2018-11-22 /pmc/articles/PMC6251163/ /pubmed/30479571 http://dx.doi.org/10.1186/s12935-018-0684-y Text en © The Author(s) 2018 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 | Primary Research Zhu, Jin-Feng Liu, Yi Huang, He Shan, Li Han, Zhi-Gang Liu, Jun-Yuan Li, Ying-Long Dong, Xiang Zeng, Wei MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
title | MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
title_full | MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
title_fullStr | MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
title_full_unstemmed | MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
title_short | MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
title_sort | microrna-133b/egfr axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251163/ https://www.ncbi.nlm.nih.gov/pubmed/30479571 http://dx.doi.org/10.1186/s12935-018-0684-y |
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