Cargando…

Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition

BACKGROUND: Emerging evidence indicates that dysregulated long intervening non-coding RNA (lincRNA) HOTAIR correlates highly with tumor invasion and metastasis but a link between the high expression of HOTAIR and the metastatic cascade of cancer stem cells (CSCs) needs to be further studied. The pur...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Jing, Chen, Dengyu, He, Xiangfeng, Zhang, Yuxia, Shi, Fangfang, Wu, Di, Chen, Junsong, Zhang, Ying, Zhao, Fengsu, Dou, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365532/
https://www.ncbi.nlm.nih.gov/pubmed/25792974
http://dx.doi.org/10.1186/s12935-015-0174-4
_version_ 1782362233049710592
author Wang, Jing
Chen, Dengyu
He, Xiangfeng
Zhang, Yuxia
Shi, Fangfang
Wu, Di
Chen, Junsong
Zhang, Ying
Zhao, Fengsu
Dou, Jun
author_facet Wang, Jing
Chen, Dengyu
He, Xiangfeng
Zhang, Yuxia
Shi, Fangfang
Wu, Di
Chen, Junsong
Zhang, Ying
Zhao, Fengsu
Dou, Jun
author_sort Wang, Jing
collection PubMed
description BACKGROUND: Emerging evidence indicates that dysregulated long intervening non-coding RNA (lincRNA) HOTAIR correlates highly with tumor invasion and metastasis but a link between the high expression of HOTAIR and the metastatic cascade of cancer stem cells (CSCs) needs to be further studied. The purpose of this study was to investigate the effect of down-regulated HOTAIR expression on tumorgeniesis and metastasis of epithelial ovarian cancer (EOC) CSCs. CD117(+)CD44(+)CSCs were isolated from human EOC SKOV3 cell line by using a magnetic-activated cell sorting system, and were then transfected with the expression vector-based small hairpin RNA targeting HOTAIR; the stably transfected cells were selected for the study. Colony-forming, wound-healing, cellular metastasis and tumorigenicity assays were performed. RESULTS: The results demonstrated that the HOTAIR expression in clinical EOC tissues and SKOV3 CD117(+)CD44(+)CSCs was higher than in SKOV3 tumor tissues and non-CD117(+)CD44(+)CSCs. The CD117(+)CD44(+)-shHOTAIR showed an inhibited HOTAIR expression, reduced cell migration and invasion than CD117(+)CD44(+)- scramble, suggesting the inhibition of an epithelial-mesenchymal transition. Moreover, the downregulated HOTAIR expression in CD117(+)CD44(+) CSCs significantly decreased the tumor growth and lung metastasis in xenograft mice. CONCLUSION: Our findings demonstrated the shHOTAIR-mediated down-regulation of the HOTAIR expression in CD117(+)CD44(+) CSCs can be a promising new opportunity for future clinical trials.
format Online
Article
Text
id pubmed-4365532
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-43655322015-03-20 Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition Wang, Jing Chen, Dengyu He, Xiangfeng Zhang, Yuxia Shi, Fangfang Wu, Di Chen, Junsong Zhang, Ying Zhao, Fengsu Dou, Jun Cancer Cell Int Primary Research BACKGROUND: Emerging evidence indicates that dysregulated long intervening non-coding RNA (lincRNA) HOTAIR correlates highly with tumor invasion and metastasis but a link between the high expression of HOTAIR and the metastatic cascade of cancer stem cells (CSCs) needs to be further studied. The purpose of this study was to investigate the effect of down-regulated HOTAIR expression on tumorgeniesis and metastasis of epithelial ovarian cancer (EOC) CSCs. CD117(+)CD44(+)CSCs were isolated from human EOC SKOV3 cell line by using a magnetic-activated cell sorting system, and were then transfected with the expression vector-based small hairpin RNA targeting HOTAIR; the stably transfected cells were selected for the study. Colony-forming, wound-healing, cellular metastasis and tumorigenicity assays were performed. RESULTS: The results demonstrated that the HOTAIR expression in clinical EOC tissues and SKOV3 CD117(+)CD44(+)CSCs was higher than in SKOV3 tumor tissues and non-CD117(+)CD44(+)CSCs. The CD117(+)CD44(+)-shHOTAIR showed an inhibited HOTAIR expression, reduced cell migration and invasion than CD117(+)CD44(+)- scramble, suggesting the inhibition of an epithelial-mesenchymal transition. Moreover, the downregulated HOTAIR expression in CD117(+)CD44(+) CSCs significantly decreased the tumor growth and lung metastasis in xenograft mice. CONCLUSION: Our findings demonstrated the shHOTAIR-mediated down-regulation of the HOTAIR expression in CD117(+)CD44(+) CSCs can be a promising new opportunity for future clinical trials. BioMed Central 2015-02-25 /pmc/articles/PMC4365532/ /pubmed/25792974 http://dx.doi.org/10.1186/s12935-015-0174-4 Text en © Wang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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.
spellingShingle Primary Research
Wang, Jing
Chen, Dengyu
He, Xiangfeng
Zhang, Yuxia
Shi, Fangfang
Wu, Di
Chen, Junsong
Zhang, Ying
Zhao, Fengsu
Dou, Jun
Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
title Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
title_full Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
title_fullStr Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
title_full_unstemmed Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
title_short Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
title_sort downregulated lincrna hotair expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365532/
https://www.ncbi.nlm.nih.gov/pubmed/25792974
http://dx.doi.org/10.1186/s12935-015-0174-4
work_keys_str_mv AT wangjing downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT chendengyu downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT hexiangfeng downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT zhangyuxia downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT shifangfang downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT wudi downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT chenjunsong downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT zhangying downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT zhaofengsu downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition
AT doujun downregulatedlincrnahotairexpressioninovariancancerstemcellsdecreasesitstumorgeniesisandmetastasisbyinhibitingepithelialmesenchymaltransition