miR-124 represses the mesenchymal features and suppresses metastasis in Ewing sarcoma
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Yunyun Li2, Gaohai Shao1, Minghua Zhang1, Fengchen Zhu1, Bo Zhao1, Chao He1, Zhongzu Zhang1
1Department of Orthopedics, the Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR China
2Department of Gynecology and Obstetrics, the Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR China
Zhongzu Zhang, email: [email protected]
Keywords: Ewing sarcoma, miR-124, SLUG, cyclin D2, mesenchymal features
Received: December 03, 2016 Accepted: December 12, 2016 Published: December 31, 2016
Metastasis is the most powerful predictor of poor outcome of Ewing sarcoma (ES). Thus, identification of new molecules involved in tumor metastasis is of crucial importance to reduce morbidity and mortality of this devastating disease. In this study, we found that miR-124, a highly conserved miRNA, was suppressed in ES tissues and might be associated with tumor metastasis through suppressing its mesenchymal features. Overexpression of miR-124 suppressed the invasion of ES cells in vitro and tumor metastasis in vivo, which might be achieved through suppressing its mesenchymal features, as overexpression of miR-124 could repress the mesenchymal genes expression, and inhibit cell differentiation to mesenchymal lineages in ES cells. However, when SLUG was experimentally restored in these cells, mesenchymal features including suppressed expression of mesenchymal genes and decreased invasive ability were observed. We also found that cyclin D2 (CCND2) was a novel target gene of miR-124, and was directly involved in miR-124-mediated suppressive effects on cell growth. Lastly, we found that treatment with 5-Aza-CdR restored the expression of miR-124, accompanied with suppressed cell proliferation, invasion and mesenchymal features of ES cells, which demonstrated that hypermethylation might be involved in the regulation of miR-124 expression. Collectively, our data suggest that hypermethylation-mediated suppression of miR-124 might be involved in the tumor initiation and metastasis through suppressing the mesenchymal features of ES cells.
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