Cancer stem cells (CSCs) have been documented to be closely related with tumor metastasis and recurrence, and the same important role were identified in Ewing Sarcoma (ES). In our previous study, we found that let-7a expression was repressed in ES. Herein, we further identified its putative effects in the CSCs of ES (ES-CSCs). The expression of let-7a was consistently suppressed in the separated side population (SP) cells, which were identified to contain the characteristics of the stem cells. Then, we increased the expression of let-7a in ES-CSCs, and found that the ability of colony formation and invasion of ES-CSCs were suppressed in vitro. The same results were found in the tumor growth of ES-CSCs’ xenograft mice in vivo. To further explore the putative mechanism involved, we also explored whether signal transducer and activator of transcription 3 (STAT3) was involved in the suppressive effects. As expected, excessive expression of let-7a could suppress the expression STAT3 in the ES-CSCs, and repressed the expression of STAT3 imitated the suppressive effects of let-7a on ES-CSCs, suppressing the ability of colony formation and invasion of ES-CSCs. Furthermore, we found lin28 was involved in the relative impacts of let-7a, as well as STAT3. Let-7a, STAT3 and lin28 might form a positive feedback circuit, which serve a pivotal role in the carcinogensis of ES-CSCs. These findings maybe provide assistance for patients with ES in the future, especially those with metastasis and recurrence, and new directions for their treatment.

癌症干细胞 (CSC) 已被证明与肿瘤转移和复发密切相关，并且在尤文肉瘤 (ES) 中也发现了同样的重要作用。在我们之前的研究中，我们发现 let-7a 表达在 ES 中被抑制。在此，我们进一步确定了其在 ES 的 CSC（ES-CSC）中的推定作用。let-7a 的表达在分离的侧群 (SP) 细胞中始终受到抑制，这些细胞被鉴定为包含干细胞的特征。然后，我们增加了 ES-CSCs 中 let-7a 的表达，发现体外抑制了 ES-CSCs 集落形成和侵袭的能力。在体内ES-CSCs 异种移植小鼠的肿瘤生长中发现了相同的结果. 为了进一步探索所涉及的假定机制，我们还探讨了信号转导和转录激活因子 3 (STAT3) 是否参与了抑制作用。正如预期的那样，let-7a 的过度表达可以抑制 ES-CSCs 中 STAT3 的表达，抑制 STAT3 的表达模拟了 let-7a 对 ES-CSCs 的抑制作用，抑制了 ES-CSCs 的集落形成和侵袭能力。 CSC。此外，我们发现 lin28 参与了 let-7a 和 STAT3 的相对影响。Let-7a、STAT3 和 lin28 可能形成正反馈回路，在 ES-CSCs 的致癌作用中起关键作用。这些发现可能为未来ES患者，特别是转移复发患者提供帮助，并为其治疗提供新的方向。