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

// Xiao-Feng Wang 1, 2, * , Xiao-Wei Zhang 1, 2, * , Rui-Xi Hua 1, 2 , Yi-Qun Du 1, 2 , Ming-Zhu Huang 1, 2 , Yong Liu 1, 2 , Yu Fang Cheng 1, 2 , Wei-Jian Guo 1, 2 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Wei-Jian Guo, email: guoweijian1@hotmail.com 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.