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The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression

Among the gynaecological cancers, epithelial ovarian cancer (EOC) has the highest lethality because of the high incidence of tumour progression and metastasis. Exploration of the detailed mechanisms underlying EOC metastasis and the identification of crucial targets is important to better estimate t...

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Autores principales: Zhang, Jing, Liu, Wenxue, Shen, Fangqian, Ma, Xiaoling, Liu, Xiaorui, Tian, Fuju, Zeng, Weihong, Xi, Xiaowei, Lin, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115398/
https://www.ncbi.nlm.nih.gov/pubmed/30158641
http://dx.doi.org/10.1038/s41419-018-0946-6
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author Zhang, Jing
Liu, Wenxue
Shen, Fangqian
Ma, Xiaoling
Liu, Xiaorui
Tian, Fuju
Zeng, Weihong
Xi, Xiaowei
Lin, Yi
author_facet Zhang, Jing
Liu, Wenxue
Shen, Fangqian
Ma, Xiaoling
Liu, Xiaorui
Tian, Fuju
Zeng, Weihong
Xi, Xiaowei
Lin, Yi
author_sort Zhang, Jing
collection PubMed
description Among the gynaecological cancers, epithelial ovarian cancer (EOC) has the highest lethality because of the high incidence of tumour progression and metastasis. Exploration of the detailed mechanisms underlying EOC metastasis and the identification of crucial targets is important to better estimate the prognosis and improve the treatment of this disease. The present study aimed to identify the role of miR-520h in the prognosis of patients with EOC, and the mechanisms of its involvement in EOC progression. We showed that miR-520h was upregulated in 116 patients with EOC, especially in those with advanced-stage disease, and high miR-520h expression predicted poor outcome. Furthermore, ectopic expression of miR-520h enhanced EOC cell proliferation, migration and invasion, and induced epithelial–mesenchymal transition in vitro and in vivo. miR-520h promoted EOC progression by downregulating Smad7, and subsequently activating the TGF-β signalling pathway. Most importantly, TGF-β1 stimulation increased miR-520h expression in EOC cells by upregulating its transcription factor c-Myb. In conclusion, we described the role of the TGF-β1/c-Myb/miR-520h/Smad7 axis in EOC metastasis, and highlighted the possible use of miR-520h as a prognostic marker for EOC.
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spelling pubmed-61153982018-08-30 The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression Zhang, Jing Liu, Wenxue Shen, Fangqian Ma, Xiaoling Liu, Xiaorui Tian, Fuju Zeng, Weihong Xi, Xiaowei Lin, Yi Cell Death Dis Article Among the gynaecological cancers, epithelial ovarian cancer (EOC) has the highest lethality because of the high incidence of tumour progression and metastasis. Exploration of the detailed mechanisms underlying EOC metastasis and the identification of crucial targets is important to better estimate the prognosis and improve the treatment of this disease. The present study aimed to identify the role of miR-520h in the prognosis of patients with EOC, and the mechanisms of its involvement in EOC progression. We showed that miR-520h was upregulated in 116 patients with EOC, especially in those with advanced-stage disease, and high miR-520h expression predicted poor outcome. Furthermore, ectopic expression of miR-520h enhanced EOC cell proliferation, migration and invasion, and induced epithelial–mesenchymal transition in vitro and in vivo. miR-520h promoted EOC progression by downregulating Smad7, and subsequently activating the TGF-β signalling pathway. Most importantly, TGF-β1 stimulation increased miR-520h expression in EOC cells by upregulating its transcription factor c-Myb. In conclusion, we described the role of the TGF-β1/c-Myb/miR-520h/Smad7 axis in EOC metastasis, and highlighted the possible use of miR-520h as a prognostic marker for EOC. Nature Publishing Group UK 2018-08-29 /pmc/articles/PMC6115398/ /pubmed/30158641 http://dx.doi.org/10.1038/s41419-018-0946-6 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Jing
Liu, Wenxue
Shen, Fangqian
Ma, Xiaoling
Liu, Xiaorui
Tian, Fuju
Zeng, Weihong
Xi, Xiaowei
Lin, Yi
The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression
title The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression
title_full The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression
title_fullStr The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression
title_full_unstemmed The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression
title_short The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression
title_sort activation of microrna-520h–associated tgf-β1/c-myb/smad7 axis promotes epithelial ovarian cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115398/
https://www.ncbi.nlm.nih.gov/pubmed/30158641
http://dx.doi.org/10.1038/s41419-018-0946-6
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