Oncotarget

Research Papers:

Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer

Xiao-Feng Wang, Xiao-Wei Zhang, Rui-Xi Hua, Yi-Qun Du, Ming-Zhu Huang, Yong Liu, Yu Fang Cheng and Wei-Jian Guo _

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Oncotarget. 2016; 7:63352-63361. https://doi.org/10.18632/oncotarget.11221

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Abstract

Xiao-Feng Wang1,2,*, Xiao-Wei Zhang1,2,*, Rui-Xi Hua1,2, Yi-Qun Du1,2, Ming-Zhu Huang1,2, Yong Liu1,2, Yu Fang Cheng1,2, Wei-Jian Guo1,2

1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Wei-Jian Guo, email: [email protected]

Keywords: Mel-18, gastric cancer, cancer stem cells, miR-21

Received: September 28, 2015    Accepted: July 16, 2016    Published: August 11, 2016

ABSTRACT

Mel-18, a polycomb group protein, has been reported to act as a tumor suppressor and be down-regulated in several human cancers including gastric cancer. It was also found that Mel-18 negatively regulates self-renewal of hematopoietic stem cells and breast cancer stem cells (CSCs). This study aimed to clarify its role in gastric CSCs and explore the mechanisms. We found that low-expression of Mel-18 was correlated with poor prognosis and negatively correlated with overexpression of stem cell markers Oct4, Sox2, and Gli1 in 101 gastric cancer tissues. Mel-18 was down-regulated in cultured spheroid cells, which possess CSCs, and overexpression of Mel-18 inhibits cells sphere-forming ability and tumor growth in vivo. Besides, Mel-18 was lower-expressed in ovary metastatic lesions compared with that in primary lesions of gastric cancer, and Mel-18 overexpression inhibited the migration ability of gastric cancer cells. Interestingly, overexpression of Mel-18 resulted in down-regulation of miR-21 in gastric cancer cells and the expression of Mel-18 was negatively correlated with the expression of miR-21 in gastric cancer tissues. Furthermore, miR-21 overexpression partially restored sphere-forming ability, migration potential and chemo-resistance in Mel-18 overexpressing gastric cancer cells. These results suggests Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer cells.


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