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

Abstract

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.

• Authors: Jing Wang, Dengyu Chen, Xiangfeng He, Yuxia Zhang, Fangfang Shi, Di Wu, Junsong Chen, Ying Zhang, Fengsu Zhao, Jun Dou
• Journal: Cancer cell international (Cancer Cell Int) Vol. 15 Pg. 24 ( 2015) ISSN: 1475-2867 [Print] England
• PMID: 25792974 (Publication Type: Journal Article)