Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing...

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Main Authors:	Wei, Shuang, Zhang, Zun-yi, Fu, Sheng-ling, Xie, Jun-gang, Liu, Xian-sheng, Xu, Yong-jian, Zhao, Jian-ping, Xiong, Wei-ning
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059863/

id	pubmed-5059863
recordtype	oai_dc
spelling	pubmed-50598632016-10-26 Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma Wei, Shuang Zhang, Zun-yi Fu, Sheng-ling Xie, Jun-gang Liu, Xian-sheng Xu, Yong-jian Zhao, Jian-ping Xiong, Wei-ning Original Article Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy. Nature Publishing Group 2016-09 2016-09-29 /pmc/articles/PMC5059863/ /pubmed/27685632 http://dx.doi.org/10.1038/cddis.2016.260 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wei, Shuang Zhang, Zun-yi Fu, Sheng-ling Xie, Jun-gang Liu, Xian-sheng Xu, Yong-jian Zhao, Jian-ping Xiong, Wei-ning
spellingShingle	Wei, Shuang Zhang, Zun-yi Fu, Sheng-ling Xie, Jun-gang Liu, Xian-sheng Xu, Yong-jian Zhao, Jian-ping Xiong, Wei-ning Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
author_facet	Wei, Shuang Zhang, Zun-yi Fu, Sheng-ling Xie, Jun-gang Liu, Xian-sheng Xu, Yong-jian Zhao, Jian-ping Xiong, Wei-ning
author_sort	Wei, Shuang
title	Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
title_short	Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
title_full	Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
title_fullStr	Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
title_full_unstemmed	Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
title_sort	hsa-mir-623 suppresses tumor progression in human lung adenocarcinoma
description	Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059863/
_version_	1613681011430785024

Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

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