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

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• 作者：Jing Wang (1)
  Dengyu Chen (2) (3)
  Xiangfeng He (4)
  Yuxia Zhang (1) (2)
  Fangfang Shi (2) (5)
  Di Wu (1) (2)
  Junsong Chen (2)
  Ying Zhang (2)
  Fengsu Zhao (2)
  Jun Dou (2)
  
  1. Department of Gynecology & Obstetrics ; Zhongda Hospital ; School of Medicine ; Southeast University ; Nanjing ; 210009 ; China
  2. Department of Pathogenic Biology and Immunology of School of Medicine ; Southeast University ; Nanjing ; 210009 ; China
  3. Bengbu Medical School ; Department of Microbiology ; Bengbu ; 233030 ; China
  4. Department of Medical Oncology ; Affiliated Tumor Hospital of Nantong University ; Nantong ; 226361 ; China
  5. Department of Oncology ; Zhongda Hospital ; Southeast University ; Nanjing ; 210009 ; China
  
• 关键词：Epithelial ovarian cancer ; Cancer stem cells ; LincRNA HOTAIR ; Epithelial ; mesenchymal transition ; RNA interference
• 刊名：Cancer Cell International
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：2,900 KB
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• 刊物主题：Cancer Research; Cell Biology;
• 出版者：BioMed Central
• ISSN：1475-2867

文摘

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.