Shen Lei, Wang Peng, Yang Jili, Li Xiaotao
Department of Anatomy, Qiqihar Medical School, Qiqihar, Heilongjiang, China.
Department of Orthopedics, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
PLoS One. 2014 Oct 7;9(10):e109138. doi: 10.1371/journal.pone.0109138. eCollection 2014.
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.
骨肉瘤是最常见的原发性骨肿瘤类型,主要影响青少年和年轻成年人。由于其发病机制复杂且对传统治疗具有抗性,骨肉瘤导致大量死亡。微小RNA是一类小的非编码RNA,通过靶向mRNA发挥关键基因调节作用,导致翻译抑制或降解。在本研究中,我们发现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水平较低与临床骨肉瘤患者的转移相关。此外,我们发现miR-217的过表达显著抑制骨肉瘤细胞的增殖、迁移和侵袭。相反,抑制miR-217表达则显著加速细胞增殖、迁移和侵袭。此外,我们确定WASF3是miR-217的一个新的功能性下游靶点。WASF3的异位表达可部分逆转miR-217对细胞增殖和侵袭的抑制作用。综上所述,我们的结果表明miR-217作为一种肿瘤抑制性微小RNA,通过靶向WASF3抑制骨肉瘤的肿瘤发生。