Liu Guangfei, Wang Lu, Han Hongmin, Li Yong, Lu Shouliang, Li Tiejun, Cheng Cai
No.1 Orthopedics Department, Cangzhou Central Hospital of Hebei Medical UniversityCangzhou, Hebei Province, China.
Am J Cancer Res. 2017 Jul 1;7(7):1450-1462. eCollection 2017.
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNAs have recently gained widespread attention and have been shown to have crucial roles in various biological regulatory processes. ZFAS1, a newly identified lncRNA, was shown to be dysregulated in several cancers. However, little is known about the alteration and functional significance of ZFAS1 in OS. In the present study, for the first time, we revealed a functional role of ZFAS1 on OS growth and metastasis. The expression of ZFAS1 was significantly overexpressed in OS samples and cell lines, and upregulation of ZFAS1 is significantly associated with unfavorable prognosis of OS patients. Functional assays also demonstrated that ZFAS1 enhanced the growth and metastatic ability of OS cells and . Mechanistically, we found that ZFAS1 positively regulated malignant phenotypes by competitively binding the miR-200b and miR-200c and upregulating BMI1. ZFAS1 also interacted with ZEB2 and regulated ZEB2 protein stability. Furthermore, we demonstrated that SP1 functions as an upstream activated factor of ZFAS1. ZFAS1 may be a potential therapeutic target for OS tumorigenesis and progression.
骨肉瘤（OS）是儿童和青少年中最常见的恶性骨肿瘤。长链非编码RNA（lncRNAs）最近受到广泛关注，并已证明在各种生物调节过程中起关键作用。ZFAS1是一种新发现的lncRNA，已证实在几种癌症中表达失调。然而，关于ZFAS1在骨肉瘤中的改变及其功能意义知之甚少。在本研究中，我们首次揭示了ZFAS1在骨肉瘤生长和转移中的功能作用。ZFAS1在骨肉瘤样本和细胞系中显著过表达，其上调与骨肉瘤患者的不良预后显著相关。功能分析还表明，ZFAS1增强了骨肉瘤细胞的生长和转移能力。机制上，我们发现ZFAS1通过竞争性结合miR-200b和miR-200c并上调BMI1来正向调节恶性表型。ZFAS1还与ZEB2相互作用并调节ZEB2蛋白稳定性。此外，我们证明SP1作为ZFAS1的上游激活因子发挥作用。ZFAS1可能是骨肉瘤发生和进展的潜在治疗靶点。
