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...
Autores principales: | , , , , , , , , , |
---|---|
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 |