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Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis

The oncoprotein EZH2, as a histone H3K27 methyltransferase, is frequently overexpressed in various cancer types. However, the mechanisms underlying its role in urinary bladder cancer (UBC) cells have not yet fully understood. Herein, we reported that honokiol, a biologically active biphenolic compou...

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Autores principales: Zhang, Qing, Zhao, Wei, Ye, Changxiao, Zhuang, Junlong, Chang, Cunjie, Li, Yuying, Huang, Xiaojing, Shen, Lan, Li, Yan, Cui, Yangyan, Song, Jiannan, Shen, Bing, Eliaz, Isaac, Huang, Ruimin, Ying, Hao, Guo, Hongqian, Yan, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741933/
https://www.ncbi.nlm.nih.gov/pubmed/26484567
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author Zhang, Qing
Zhao, Wei
Ye, Changxiao
Zhuang, Junlong
Chang, Cunjie
Li, Yuying
Huang, Xiaojing
Shen, Lan
Li, Yan
Cui, Yangyan
Song, Jiannan
Shen, Bing
Eliaz, Isaac
Huang, Ruimin
Ying, Hao
Guo, Hongqian
Yan, Jun
author_facet Zhang, Qing
Zhao, Wei
Ye, Changxiao
Zhuang, Junlong
Chang, Cunjie
Li, Yuying
Huang, Xiaojing
Shen, Lan
Li, Yan
Cui, Yangyan
Song, Jiannan
Shen, Bing
Eliaz, Isaac
Huang, Ruimin
Ying, Hao
Guo, Hongqian
Yan, Jun
author_sort Zhang, Qing
collection PubMed
description The oncoprotein EZH2, as a histone H3K27 methyltransferase, is frequently overexpressed in various cancer types. However, the mechanisms underlying its role in urinary bladder cancer (UBC) cells have not yet fully understood. Herein, we reported that honokiol, a biologically active biphenolic compound isolated from the Magnolia officinalis inhibited human UBC cell proliferation, survival, cancer stemness, migration, and invasion, through downregulation of EZH2 expression level, along with the reductions of MMP9, CD44, Sox2 and the induction of tumor suppressor miR-143. Either EZH2 overexpression or miR-143 inhibition could partially reverse honokiol-induced cell growth arrest and impaired clonogenicity. Importantly, it was first revealed that EZH2 could directly bind to the transcriptional regulatory region of miR-143 and repress its expression. Furthermore, honokiol treatment on T24 tumor xenografts confirmed its anticancer effects in vivo, including suppression tumor growth and tumor stemness, accompanied by the dysregulation of EZH2 and miR-143 expressions. Our data suggest a promising therapeutic option to develop drugs targeting EZH2/miR-143 axis, such as honokiol, for bladder cancer treatment.
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spelling pubmed-47419332016-03-17 Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis Zhang, Qing Zhao, Wei Ye, Changxiao Zhuang, Junlong Chang, Cunjie Li, Yuying Huang, Xiaojing Shen, Lan Li, Yan Cui, Yangyan Song, Jiannan Shen, Bing Eliaz, Isaac Huang, Ruimin Ying, Hao Guo, Hongqian Yan, Jun Oncotarget Research Paper The oncoprotein EZH2, as a histone H3K27 methyltransferase, is frequently overexpressed in various cancer types. However, the mechanisms underlying its role in urinary bladder cancer (UBC) cells have not yet fully understood. Herein, we reported that honokiol, a biologically active biphenolic compound isolated from the Magnolia officinalis inhibited human UBC cell proliferation, survival, cancer stemness, migration, and invasion, through downregulation of EZH2 expression level, along with the reductions of MMP9, CD44, Sox2 and the induction of tumor suppressor miR-143. Either EZH2 overexpression or miR-143 inhibition could partially reverse honokiol-induced cell growth arrest and impaired clonogenicity. Importantly, it was first revealed that EZH2 could directly bind to the transcriptional regulatory region of miR-143 and repress its expression. Furthermore, honokiol treatment on T24 tumor xenografts confirmed its anticancer effects in vivo, including suppression tumor growth and tumor stemness, accompanied by the dysregulation of EZH2 and miR-143 expressions. Our data suggest a promising therapeutic option to develop drugs targeting EZH2/miR-143 axis, such as honokiol, for bladder cancer treatment. Impact Journals LLC 2015-10-15 /pmc/articles/PMC4741933/ /pubmed/26484567 Text en Copyright: © 2015 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Qing
Zhao, Wei
Ye, Changxiao
Zhuang, Junlong
Chang, Cunjie
Li, Yuying
Huang, Xiaojing
Shen, Lan
Li, Yan
Cui, Yangyan
Song, Jiannan
Shen, Bing
Eliaz, Isaac
Huang, Ruimin
Ying, Hao
Guo, Hongqian
Yan, Jun
Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
title Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
title_full Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
title_fullStr Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
title_full_unstemmed Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
title_short Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
title_sort honokiol inhibits bladder tumor growth by suppressing ezh2/mir-143 axis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741933/
https://www.ncbi.nlm.nih.gov/pubmed/26484567
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