Department of Orthopedics Trauma, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, P.R. China.
Department of Orthopedics, Zaozhuang Hospital of ZaoZhuang Mining Group, ZaoZhuang, Shandong, P.R. China.
Sci Prog. 2021 Apr-Jun;104(2):368504211002043. doi: 10.1177/00368504211002043.
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.
尤因肉瘤（ES）是一种主要发生在儿童身上的恶性肿瘤。然而，ES 的潜在机制仍不清楚。通过分析之前两份 miRNA 芯片报告的结果，我们发现 miR-146b-5p 可能是 ES 进展中的一种癌基因 miRNA。为了验证这一假说，我们通过实时 PCR 检测了 miR-146b-5p 的表达水平，并通过 CCK8 和 Transwell 测定观察了 miR-146b-5p 对 ES 细胞进展的影响。生物信息学和荧光素酶报告基因实验用于鉴定 miR-146b-5p 的靶基因。结果表明，与人类间充质干细胞（MSCs）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 的上调或下调分别能有效促进或阻断 ES 细胞的增殖、迁移和侵袭。此外，我们证实 BTG2 是 miR-146b-5p 的靶基因之一，并介导了 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 的治疗提供新的思路。
