Osteosarcoma is one of the most malignant cancer adolescents and young adults and metastatic osteosarcoma is a huge life threat with a 5-year survival lower than 20%. However, the mechanisms through which localized osteosarcoma turned metastatic are not fully understood. Here, we studied the role of miR-204-5p in osteosarcoma and found that miR-204-5p is downregulated in both osteosarcoma patients and osteosarcoma cell lines. In addition, overexpression of miR-204-5p resulted in increase of osteosarcoma cell apoptosis and decrease of osteosarcoma cell migration and invasion. Besides, our in vivo xenograft data showed strong inhibitory role of miR-204-5p in tumor growth. Importantly, our data showed that miR-204-5p regulates the mRNA stability of Early B Cell Factor 2 (EBF2), a crucial regulator in osteosarcoma apoptosis, by directly binding to 3’ UTR of EBF2. Besides, our data further revealed that overexpressed EBF2 inhibited apoptosis and facilitated migration and invasion of osteosarcoma cells. Additionally, EBF2 overexpression rescued the phenotype caused by miR-204-5p.Our data indicated that miR-204-5p is an anti-oncogenic miRNA in osteosarcoma which functions through inhibiting oncogenic transcription factor EBF2. These results provided new therapeutic targets for metastatic osteosarcoma and insights into molecular regulation of EBF2.

骨肉瘤是青少年和年轻人中最恶性的癌症之一，转移性骨肉瘤是巨大的生命威胁，其5年生存率低于20％。但是，局部骨肉瘤转变为转移的机制尚不完全清楚。在这里，我们研究了miR-204-5p在骨肉瘤中的作用，发现miR-204-5p在骨肉瘤患者和骨肉瘤细胞系中均下调。此外，miR-204-5p的过表达导致骨肉瘤细胞凋亡增加，并减少骨肉瘤细胞迁移和侵袭。此外，我们的体内异种移植数据显示miR-204-5p在肿瘤生长中具有强大的抑制作用。重要的是，我们的数据表明miR-204-5p通过直接结合EBF2的3'UTR来调节早期B细胞因子2（EBF2）的mRNA稳定性，EBF2是骨肉瘤凋亡中的关键调节剂。此外，我们的数据进一步揭示，过表达的EBF2抑制凋亡并促进骨肉瘤细胞的迁移和侵袭。此外，EBF2的过表达挽救了miR-204-5p引起的表型。我们的数据表明，miR-204-5p是骨肉瘤中的一种抗癌miRNA，可通过抑制致癌转录因子EBF2发挥作用。这些结果为转移性骨肉瘤提供了新的治疗靶点，并为EBF2的分子调控提供了见识。