Osteosarcoma remains fatal in adolescents and young adults, with a 5-year survival rate of less than 20%. However, the details for mechanisms that regulate osteosarcoma metastasis are poorly understood. We analyzed the expression levels of miR-211-5p in clinical samples of osteosarcoma as well as cell lines, and found that the expression of miR-211-5p was reduced in osteosarcoma. Moreover, induction of miR-211-5p in several osteosarcoma cell lines dramatically inhibited their migration and invasiveness. Furthermore, miR-211-5p overexpression led to a significant increase in the apoptosis of osteosarcoma cell. Importantly, our in vivo xenograft experiments showed that miR-211-5p strongly inhibits tumorigenesis. Additionally, functional experiments demonstrated that miR-211-5p suppresses the expression of proline-rich protein 11 (PRR11) by directly binding to the 3' region of PRR11 mRNA. Moreover, we showed that PRR11 overexpression attenuated the increase of apoptosis and decreased migration and invasiveness when the upstream miR-211-5p was overexpressed. Our data provide new insights into the mechanisms that regulate osteosarcoma metastasis, and novel potential pharmaceutical targets for personalized medicine.

中文翻译：

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MicroRNA-211-5p通过靶向富含脯氨酸的蛋白PRR11促进细胞凋亡并抑制骨肉瘤细胞的迁移。

骨肉瘤在青少年和年轻人中仍然是致命的，其5年生存率不到20％。但是，对于调节骨肉瘤转移的机制的细节了解甚少。我们分析了骨肉瘤临床样本以及细胞系中miR-211-5p的表达水平，发现miR-211-5p在骨肉瘤中的表达降低。而且，在几种骨肉瘤细胞系中miR-211-5p的诱导极大地抑制了它们的迁移和侵袭性。此外，miR-211-5p过表达导致骨肉瘤细胞凋亡的显着增加。重要的是，我们的体内异种移植实验表明miR-211-5p强烈抑制肿瘤发生。另外，功能实验表明，miR-211-5p通过直接结合PRR11 mRNA的3'区域来抑制富含脯氨酸的蛋白11（PRR11）的表达。此外，我们显示，当上游miR-211-5p过表达时，PRR11的过表达减弱了细胞凋亡的增加，并减少了迁移和侵袭性。我们的数据为调节骨肉瘤转移的机制提供了新见识，并为个性化药物提供了新的潜在药物靶标。