Department of Orthopaedics, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China.
Department of Radiology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China.
Biochem Biophys Res Commun. 2019 Mar 26;511(1):63-68. doi: 10.1016/j.bbrc.2019.02.007. Epub 2019 Feb 11.
Aberrant miRNAs play important roles in tumor development and progression. Previous studies reported that miR-552 was dysregulated expressed in multiple cancers. However, its biological effects and underlying mechanism in osteosarcoma remains largely unknown. In present research, we demonstrated that miR-552 was significantly up-regulated in both osteosarcoma cell lines and tissues for the first time. Its high-expression was significantly associated with poor prognostic features and overall survival of osteosarcoma patients. Gain- and loss-of-function experiment confirmed that miR-552 promoted cell migration, invasion and MMPs expression. Moreover, TIMP2 was a direct downstream target of miR-552. miR-552 inversely correlated with TIMP2 in osteosarcoma tissues. TIMP2 restoration at least partially abolished the migration, invasion and MMPs expression of miR-552 on osteosarcoma cells. Above all, our data suggest that miR-552 promoted migration, invasion and MMPs expression of osteosarcoma by targeting TIMP2, and represent a novel potential therapeutic target for osteosarcoma.
异常表达的 miRNAs 在肿瘤的发生和发展中起着重要作用。先前的研究报道 miR-552 在多种癌症中表达失调。然而，其在骨肉瘤中的生物学功能和潜在机制尚不清楚。在本研究中，我们首次证明 miR-552 在骨肉瘤细胞系和组织中均呈显著上调。其高表达与骨肉瘤患者的不良预后特征和总生存期显著相关。增益和缺失功能实验证实 miR-552 促进了细胞迁移、侵袭和 MMPs 的表达。此外，TIMP2 是 miR-552 的直接下游靶基因。miR-552 在骨肉瘤组织中与 TIMP2 呈负相关。TIMP2 的恢复至少部分消除了 miR-552 对骨肉瘤细胞迁移、侵袭和 MMPs 表达的影响。综上所述，我们的数据表明，miR-552 通过靶向 TIMP2 促进骨肉瘤的迁移、侵袭和 MMPs 表达，代表了骨肉瘤治疗的一个新的潜在靶点。
