Cargando…
MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma
PURPOSE: Accumulating evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. In this study, we aimed to identify the role of miR-27a in esophageal squamous cell carcinoma (ESCC) radiosensitivity by exploring the relationship between miR-27a and he...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661375/ https://www.ncbi.nlm.nih.gov/pubmed/31413593 http://dx.doi.org/10.2147/OTT.S197456 |
_version_ | 1783439436711723008 |
---|---|
author | Wang, Xintong An, Dianzheng Liu, Xiaomeng Wang, Xinlei Li, Baosheng |
author_facet | Wang, Xintong An, Dianzheng Liu, Xiaomeng Wang, Xinlei Li, Baosheng |
author_sort | Wang, Xintong |
collection | PubMed |
description | PURPOSE: Accumulating evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. In this study, we aimed to identify the role of miR-27a in esophageal squamous cell carcinoma (ESCC) radiosensitivity by exploring the relationship between miR-27a and heat shock protein 90 (Hsp90). MATERIALS AND METHODS: We performed quantitative real-time polymerase chain reaction (qRT-PCR) to detect miR-27a expression in the plasma of ESCC patients and healthy volunteers. The expression of Hsp90 and its key client proteins associated with radioresistance were analyzed by Western blotting. Then, the effects of miR-27a on proliferation, apoptosis, cell cycle and radiosensitivity in ESCC cell lines were determined by CCK-8, flow cytometry, and clonogenic survival assay. We also generated subcutaneous tumors to explore whether miR-27a enhanced radiosensitivity in vivo. RESULTS: In our current study, we found that miR-27a expression was downregulated in the plasma of ESCC patients compared with that of healthy volunteers. Overexpression of miR-27a in ESCC cell lines caused a reduction of Hsp90 mRNA and protein. We also demonstrated that upregulation of miR-27a induced degradation of Hsp90 key client proteins associated with radioresistance. In related functional experiments, miR-27a significantly inhibited growth, increased radiation-induced apoptosis, induced cell cycle arrest in G(0)/G(1) phase and enhanced ESCC radiosensitivity both in vitro and in vivo. CONCLUSION: From these findings, we concluded that miR-27a may contribute to radiosensitivity by modulating Hsp90 expression. Moreover, miR-27a-based therapy utilized to target Hsp90 could be contemplated as a compelling alternative for sensitize ESCC to radiotherapy with fewer side effects. |
format | Online Article Text |
id | pubmed-6661375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-66613752019-08-14 MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma Wang, Xintong An, Dianzheng Liu, Xiaomeng Wang, Xinlei Li, Baosheng Onco Targets Ther Original Research PURPOSE: Accumulating evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. In this study, we aimed to identify the role of miR-27a in esophageal squamous cell carcinoma (ESCC) radiosensitivity by exploring the relationship between miR-27a and heat shock protein 90 (Hsp90). MATERIALS AND METHODS: We performed quantitative real-time polymerase chain reaction (qRT-PCR) to detect miR-27a expression in the plasma of ESCC patients and healthy volunteers. The expression of Hsp90 and its key client proteins associated with radioresistance were analyzed by Western blotting. Then, the effects of miR-27a on proliferation, apoptosis, cell cycle and radiosensitivity in ESCC cell lines were determined by CCK-8, flow cytometry, and clonogenic survival assay. We also generated subcutaneous tumors to explore whether miR-27a enhanced radiosensitivity in vivo. RESULTS: In our current study, we found that miR-27a expression was downregulated in the plasma of ESCC patients compared with that of healthy volunteers. Overexpression of miR-27a in ESCC cell lines caused a reduction of Hsp90 mRNA and protein. We also demonstrated that upregulation of miR-27a induced degradation of Hsp90 key client proteins associated with radioresistance. In related functional experiments, miR-27a significantly inhibited growth, increased radiation-induced apoptosis, induced cell cycle arrest in G(0)/G(1) phase and enhanced ESCC radiosensitivity both in vitro and in vivo. CONCLUSION: From these findings, we concluded that miR-27a may contribute to radiosensitivity by modulating Hsp90 expression. Moreover, miR-27a-based therapy utilized to target Hsp90 could be contemplated as a compelling alternative for sensitize ESCC to radiotherapy with fewer side effects. Dove 2019-07-23 /pmc/articles/PMC6661375/ /pubmed/31413593 http://dx.doi.org/10.2147/OTT.S197456 Text en © 2019 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Xintong An, Dianzheng Liu, Xiaomeng Wang, Xinlei Li, Baosheng MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
title | MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
title_full | MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
title_fullStr | MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
title_full_unstemmed | MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
title_short | MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
title_sort | microrna-27a downregulates the expression of hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661375/ https://www.ncbi.nlm.nih.gov/pubmed/31413593 http://dx.doi.org/10.2147/OTT.S197456 |
work_keys_str_mv | AT wangxintong microrna27adownregulatestheexpressionofhsp90andenhancestheradiosensitivityinesophagealsquamouscellcarcinoma AT andianzheng microrna27adownregulatestheexpressionofhsp90andenhancestheradiosensitivityinesophagealsquamouscellcarcinoma AT liuxiaomeng microrna27adownregulatestheexpressionofhsp90andenhancestheradiosensitivityinesophagealsquamouscellcarcinoma AT wangxinlei microrna27adownregulatestheexpressionofhsp90andenhancestheradiosensitivityinesophagealsquamouscellcarcinoma AT libaosheng microrna27adownregulatestheexpressionofhsp90andenhancestheradiosensitivityinesophagealsquamouscellcarcinoma |