MicroRNA-217 Regulates WASF3 Expression and Suppresses Tumor Growth and Metastasis in Osteosarcoma

Osteosarcoma is the most common type of primary tumor of bone which mainly affects adolescents and young adults. Osteosarcoma causes large number of deaths because of its complex pathogenesis and resistance to conventional treatment. MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs, causing translational repression or degradation. In this study, we showed that miR-217 was down-regulated in osteosarcoma cell lines and tissues in comparison to that in normal bone cells or tissues. Meanwhile, the lower level of miR-217 was associated with metastasis in clinical osteosarcoma patients. Furthermore, we found that overexpession of miR-217 markedly suppressed cell proliferation, migration, and invasion of osteosarcoma cells. Conversely, the inhibition of miR-217 expression significantly accelerated the cell proliferation, migration, and invasion. Moreover, we identified WASF3 as a novel functional downstream target of miR-217. The ectopic expression of WASF3 can partially reverse the inhibition of cell proliferation and invasion caused by miR-217. Take together, our results demonstrate that miR-217 functions as a tumor-suppressive miRNA and inhibits the osteosarcoma tumorigenesis through targeting WASF3.

骨肉瘤是骨骼原发肿瘤中最常见的一种，主要影响青少年及年轻成年人。由于其复杂的发病机制和对传统治疗的抵抗性，骨肉瘤导致大量死亡。微RNA是一类小型非编码RNA，通过靶向mRNA，作为关键的基因调控因子，导致翻译抑制或降解。在本研究中，我们揭示了与正常骨细胞或组织相比，miR-217在骨肉瘤细胞系和组织中表达下调。同时，miR-217水平的降低与临床骨肉瘤患者的转移相关。此外，我们发现miR-217的过表达显著抑制了骨肉瘤细胞的增殖、迁移和侵袭。相反，miR-217表达的抑制显著加速了细胞的增殖、迁移和侵袭。此外，我们鉴定了WASF3为miR-217的一个新的功能性下游靶点。WASF3的异位表达可以部分逆转由miR-217引起的细胞增殖和侵袭的抑制。综合来看，我们的研究结果证实了miR-217作为一种肿瘤抑制性miRNA，通过靶向WASF3抑制骨肉瘤的肿瘤发生。