MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell

BMC Cancer

Yuhua Lu²  Jingjing Lu³  Xiaohong Li³  Hui Zhu³  Xiangjun Fan¹  Shajun Zhu¹  Yao Wang¹  Qingsong Guo¹  Lei Wang¹  Yan Huang¹  Mingyan Zhu¹  Zhiwei Wang¹ 

[1] Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, P. R. China

[2] Visitor scholar of Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA

[3] Surgical comprehensive laboratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, P. R. China

关键词: miR-200a;    Pancreatic cancer;    EMT;    CSC;   

Others  :  859072
DOI  :  10.1186/1471-2407-14-85

 received in 2013-08-12, accepted in 2014-01-27,  发布年份 2014

【 摘 要 】

Background

Pancreatic cancer is one of the most aggressive cancers, and the aggressiveness of pancreatic cancer is in part due to its intrinsic and extrinsic drug resistance characteristics, which are also associated with the acquisition of epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. And miR-200 has been identified as a powerful regulator of EMT.

Methods

Cancer Stem Cells (CSCs) of human pancreatic cancer cell line PANC-1 were processed for CD24, CD44 and ESA multi-colorstaining, and sorted out on a BD FACS Aria II machine. RT-qPCR was performed using the miScript PCR Kit to assay the expression of miR-200 family. In order to find the role of miR-200a in the process of EMT, miR-200a mimic was transfected to CSCs.

Results

Pancreatic cancer cells with EMT phenotype displayed stem-like cell features characterized by the expression of cell surface markers CD24, CD44 and epithelial-specific antigen (ESA), which was associated with decreased expression of miR-200a. Moreover, overexpression of miR-200a was resulted in down-regulation of N-cadherin, ZEB1 and vimentin, but up-regulation of E-cadherin. In addition, miR-200a overexpression inhibited cell migration and invasion in CSCs.

Conclusion

In our study, we found that miR-200a played an important role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in pancreatic cancer. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to mesenchymal-to-epithelial transition (MET) phenotype using novel agents would be useful for prevention and/or treatment of pancreatic cancer.

【 授权许可】

   
2014 Lu et al.; licensee BioMed Central Ltd.

【 图 表 】

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