Ewing sarcoma (ES) is a malignant tumor that occurs mostly in children. However, the underlying mechanisms of ES are still unknown. Analyzing the results of two previous miRNA array reports, we found that miR-146b-5p might be an onco-miRNA in ES progression. To test this hypothesis, we detected the expression levels of miR-146b-5p by real-time PCR and observed the effects of miR-146b-5p on the progression of ES cells by CCK8 and transwell assays. Bioinformatics and luciferase assays were used to identify the target genes of miR-146b-5p. It showed that the expression levels of miR-146b-5p were upregulated in ES cell lines compared with human mesenchymal stem cells (MSCs). Up- or downregulation of miR-146b-5p in ES cell lines could effectively promote or block the proliferation, migration, and invasion of ES cells, respectively. Furthermore, we demonstrated that BTG2 was one of the target genes and mediated the effects of miR-146b-5p in ES cells. Interestingly, we also found that miR-146b-5p was partly involved in the anticancer effects of pemetrexed in ES cells. Our study revealed that miR-146b-5p affected the progression of ES by suppressing BTG2, which might shed light on anticancer drug development and ES treatment in the future.

尤文肉瘤（ES）是一种多发于儿童的恶性肿瘤。然而，ES的潜在机制仍不清楚。分析之前两篇 miRNA 芯片报告的结果，我们发现 miR-146b-5p 可能是 ES 进展中的癌 miRNA。为了验证这一假设，我们通过实时PCR检测了miR-146b-5p的表达水平，并通过CCK8和transwell实验观察了miR-146b-5p对ES细胞进展的影响。使用生物信息学和荧光素酶测定来鉴定 miR-146b-5p 的靶基因。结果表明，与人间充质干细胞（MSC）相比，ES细胞系中miR-146b-5p的表达水平上调。ES细胞系中miR-146b-5p的上调或下调可分别有效促进或阻断ES细胞的增殖、迁移和侵袭。此外，我们证明 BTG2 是靶基因之一，并介导 miR-146b-5p 在 ES 细胞中的作用。有趣的是，我们还发现miR-146b-5p部分参与了培美曲塞在ES细胞中的抗癌作用。我们的研究表明，miR-146b-5p通过抑制BTG2影响ES的进展，这可能为未来抗癌药物的开发和ES治疗带来启示。