MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition

Journal of Ovarian Research

Jun Dou²  Fangfang Shi¹  Xiaoying Wang²  Kai Cai²  Cuiping Yang²  Junsong Chen²  Jing Wang⁴  Yunxia Zhang⁴  Dengyu Chen³ 

[1] Department of Oncology, Zhongda Hospital, Southeast University, Nanjing 210009, China;Department of Pathogenic Biology and Immunology of Medical College, Southeast University, Nanjing 210009, China;Department of Microbiology, Bengbu Medical School, Bengbu 233030, China;Department of Gynecology & Obstetrics, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China

关键词: Metastasis;    Epithelial- mesenchymal transition;    MiRNAs-200c;    Cancer stem cells;    Epithelial ovarian cancer;   

Others  :  820662
DOI  :  10.1186/1757-2215-6-50

 received in 2013-05-16, accepted in 2013-06-23,  发布年份 2013

【 摘 要 】

Background

Cancer stem cells (CSCs) are believed to be ‘seed cell’ in cancer recurrence and metastasis. MicroRNAs (miRNAs) can play an important role in the progression of primary tumor towards metastasis by regulating the epithelial-mesenchymal transition (EMT). The goal of this study was to investigate the effect of miRNA-200c overexpression on the EMT, tumorigenicity and metastasis of epithelial ovarian cancer (EOC) CSCs.

Methods

The EOC CD117⁺CD44⁺CSCs were isolated from the human ovarian cancer cell line SKOV3 by using a magnetic-activated cell sorting system, and the lentivirus miR-200c transduced CSCs were then selected for the study. The assays of colony forming, wound healing, cellular migration in vitro and tumor progression in vivo were performed.

Results

The miR-200c expression was reduced in the CD117⁺CD44⁺CSCs compared with the non-CD117⁺CD44⁺CSCs. However, the stable overexpression of the miR-200c in the CD117⁺CD44⁺CSCs resulted in a significant down-regulation of ZEB-1 and the Vimentin expression, an upregulation of the E-cadherin expression as well as a decrease of colony forming, migratory and invasion in vitro. Importantly, the miR-200c overexpression significantly inhibited the CD117⁺CD44⁺CSCs xenograft growth and lung metastasis in vivo in nude mice by inhibition of the EMT. In addition, the down-regulation of ZEB-1 showed the same efficacy as the miR-200c overexpression in the CD117⁺CD44⁺CSCs.

Conclusion

These findings from this study suggest that the miR-200c overexpression may be considered a critical approach for the EOC CD117⁺CD44⁺CSCs in clinical trials.

【 授权许可】

   
2013 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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