MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma

Xintong Wang,1,2 Dianzheng An,1 Xiaomeng Liu,3 Xinlei Wang,4 Baosheng Li11Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, The Affiliated Hospita...

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Main Authors: Wang X, An D, Liu X, Li B
Format: Article
Language:English
Published: Dove Medical Press 2019-07-01
Series:OncoTargets and Therapy
Subjects:
Online Access:https://www.dovepress.com/microrna-27a-downregulates-the-expression-of-hsp90-and-enhances-the-ra-peer-reviewed-article-OTT
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spelling doaj-6c392ba2bb6e4b7e92db3aa328897ca22020-11-25T01:55:21ZengDove Medical PressOncoTargets and Therapy1178-69302019-07-01Volume 125967597747343MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinomaWang XAn DLiu XWang XLi BXintong Wang,1,2 Dianzheng An,1 Xiaomeng Liu,3 Xinlei Wang,4 Baosheng Li11Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3University of Jinan, School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 4Department of Gastroenterology, Qingdao Hiser Medical Center, Qingdao, Shandong, People’s Republic of ChinaPurpose: 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 G0/G1 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.Keywords: miR-27a, Hsp90, esophageal squamous cell carcinoma, radiosensitivityhttps://www.dovepress.com/microrna-27a-downregulates-the-expression-of-hsp90-and-enhances-the-ra-peer-reviewed-article-OTTmiR-27aHsp90esophageal squamous cell carcinomaradiosensitivity
collection DOAJ
language English
format Article
sources DOAJ
author Wang X
An D
Liu X
Wang X
Li B
spellingShingle Wang X
An D
Liu X
Wang X
Li B
MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma
OncoTargets and Therapy
miR-27a
Hsp90
esophageal squamous cell carcinoma
radiosensitivity
author_facet Wang X
An D
Liu X
Wang X
Li B
author_sort Wang X
title 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_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_sort microrna-27a downregulates the expression of hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma
publisher Dove Medical Press
series OncoTargets and Therapy
issn 1178-6930
publishDate 2019-07-01
description Xintong Wang,1,2 Dianzheng An,1 Xiaomeng Liu,3 Xinlei Wang,4 Baosheng Li11Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3University of Jinan, School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 4Department of Gastroenterology, Qingdao Hiser Medical Center, Qingdao, Shandong, People’s Republic of ChinaPurpose: 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 G0/G1 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.Keywords: miR-27a, Hsp90, esophageal squamous cell carcinoma, radiosensitivity
topic miR-27a
Hsp90
esophageal squamous cell carcinoma
radiosensitivity
url https://www.dovepress.com/microrna-27a-downregulates-the-expression-of-hsp90-and-enhances-the-ra-peer-reviewed-article-OTT
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