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miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer

BACKGROUND: Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of...

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Autores principales: Yu, Xiaotang, Zhang, Xinchen, Wang, Guang, Wang, Bo, Ding, Yanfang, Zhao, Jinyao, Liu, Hanlin, Cui, Shiying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641844/
https://www.ncbi.nlm.nih.gov/pubmed/33292230
http://dx.doi.org/10.1186/s12935-020-01623-y
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author Yu, Xiaotang
Zhang, Xinchen
Wang, Guang
Wang, Bo
Ding, Yanfang
Zhao, Jinyao
Liu, Hanlin
Cui, Shiying
author_facet Yu, Xiaotang
Zhang, Xinchen
Wang, Guang
Wang, Bo
Ding, Yanfang
Zhao, Jinyao
Liu, Hanlin
Cui, Shiying
author_sort Yu, Xiaotang
collection PubMed
description BACKGROUND: Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. METHODS: MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. RESULTS: miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. CONCLUSION: miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.
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spelling pubmed-76418442020-11-05 miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer Yu, Xiaotang Zhang, Xinchen Wang, Guang Wang, Bo Ding, Yanfang Zhao, Jinyao Liu, Hanlin Cui, Shiying Cancer Cell Int Primary Research BACKGROUND: Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. METHODS: MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. RESULTS: miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. CONCLUSION: miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction. BioMed Central 2020-11-03 /pmc/articles/PMC7641844/ /pubmed/33292230 http://dx.doi.org/10.1186/s12935-020-01623-y Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Primary Research
Yu, Xiaotang
Zhang, Xinchen
Wang, Guang
Wang, Bo
Ding, Yanfang
Zhao, Jinyao
Liu, Hanlin
Cui, Shiying
miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
title miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
title_full miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
title_fullStr miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
title_full_unstemmed miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
title_short miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
title_sort mir-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641844/
https://www.ncbi.nlm.nih.gov/pubmed/33292230
http://dx.doi.org/10.1186/s12935-020-01623-y
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