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Overexpression of miR-200a suppresses epithelial-mesenchymal transition of liver cancer stem cells

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Tumor Biology

Abstract

Due to high incidence of invasion and intrahepatic metastasis, hepatocellular carcinoma (HCC) is one of the most aggressive tumors in the world, which is also associated with the acquisition of epithelial-mesenchymal transition (EMT). Increasing evidence suggests that cancer cells with EMT traits share many biological characteristics with cancer stem cells. And miR-200a has been known as a powerful regulator of EMT. Here, we sought to investigate the role of miR-200a in regulation of EMT phenotype of liver cancer stem cells (LCSCs). We used side population (SP) sorting to obtain cancer stem-like cells from HCC cell lines and identified that the SP fraction could be enriched with LCSCs. Then, we detected the expression of miR-200a and EMT makers in SP and non-SP cells. Our results suggested that miR-200a was down-regulated in SP cells, along with relatively low epithelial marker and high mesenchymal marker. In order to find the role of miR-200a in the manipulation of EMT, we transfected miR-200a mimic into LCSCs and found that overexpression of miR-200a resulted in down-regulation of N-cadherin, ZEB2, and vimentin, but up-regulation of E-cadherin. Moreover, overexpression of miR-200a resulted in decreased migration and invasion ability in LCSCs. In conclusion, our study revealed that miR-200a played an important role in linking the characteristics of cancer stem cells with EMT phenotype in HCC, and targeting miR-200a might be an effective strategy to weaken the invasive behavior of LCSCs.

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Acknowledgments

We are grateful to Fuqin Zhang who provided technical support. This work was supported by the National Natural Science Foundation of China (grant no. 81172061 and 81401940)

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Changle Street, Xi’an, Shaan xi, 710032, China

    Jianlin Wang, Xisheng Yang, Bai Ruan, Bin Dai, Yuan Gao, Juanli Duan, Shibin Qu, Kaishan Tao, Kefeng Dou & Haimin Li

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  1. Jianlin Wang
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  2. Xisheng Yang
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  3. Bai Ruan
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  4. Bin Dai
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  7. Shibin Qu
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  10. Haimin Li
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Correspondence to Haimin Li.

Additional information

Jianlin Wang, Xisheng Yang, and Bai Ruan contributed equally to this work and should be recognized as co-first authors.

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Wang, J., Yang, X., Ruan, B. et al. Overexpression of miR-200a suppresses epithelial-mesenchymal transition of liver cancer stem cells. Tumor Biol. 36, 2447–2456 (2015). https://doi.org/10.1007/s13277-014-2856-2

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  • DOI: https://doi.org/10.1007/s13277-014-2856-2

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