Han Feng, Wang Changhe, Wang Yi, Zhang Liang
Department of Orthopedics, First People' Hospital of ShangqiuShangqiu 476100, Henan, China.
Department of Radiology, Zhumadian Central HospitalZhumadian 463000, Henan, China.
Am J Cancer Res. 2017 Apr 1;7(4):770-783. eCollection 2017.
Long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) is a novel lncRNA, which is recently reported to have critical roles in carcinogenesis and progression of several cancers. However, the expression, clinical values, biological roles, and underlying molecular mechanisms of lncRNA-ATB in osteosarcoma are still known. In this study, we measured lncRNA-ATB expression in serum and osteosarcoma tissues of osteosarcoma patients, analyzed its diagnostic and prognostic values. Serum lncRNA-ATB is increased in osteosarcoma patients and could accurately discriminate osteosarcoma patients from healthy controls. LncRNA-ATB is also upregulated in osteosarcoma tissues and cell lines, and positively associated with Enneking stage, metastasis and recurrence. Increased lncRNA-ATB level indicates poor recurrence-free survival and overall survival. Functional experiments demonstrated that overexpression of lncRNA-ATB enhances osteosarcoma cells proliferation, migration, and invasion, and while depletion of lncRNA-ATB inhibits osteosarcoma cells proliferation, migration, and invasion. Mechanistically, we found that lncRNA-ATB inhibits miR-200s, and upregulates miR-200s target genes ZEB1 and ZEB2. Additionally, the roles of lncRNA-ATB on osteosarcoma cells proliferation, migration, and invasion , and osteosarcoma tumor growth are dependent on the regulation of miR-200s. Taken together, this study suggests that lncRNA-ATB may be a potential diagnostic and prognostic biomarker and a therapeutic target for osteosarcoma.
转化生长因子-β激活的长链非编码RNA（lncRNA-ATB）是一种新型的长链非编码RNA，最近有报道称其在多种癌症的发生和发展中起关键作用。然而，lncRNA-ATB在骨肉瘤中的表达、临床价值、生物学作用及潜在分子机制仍不清楚。在本研究中，我们检测了骨肉瘤患者血清和骨肉瘤组织中lncRNA-ATB的表达，分析了其诊断和预后价值。骨肉瘤患者血清lncRNA-ATB升高，且能准确区分骨肉瘤患者与健康对照。lncRNA-ATB在骨肉瘤组织和细胞系中也上调，并与Enneking分期、转移和复发呈正相关。lncRNA-ATB水平升高表明无复发生存期和总生存期较差。功能实验表明，lncRNA-ATB过表达增强骨肉瘤细胞的增殖、迁移和侵袭，而lncRNA-ATB缺失则抑制骨肉瘤细胞的增殖、迁移和侵袭。机制上，我们发现lncRNA-ATB抑制miR-200s，并上调miR-200s的靶基因ZEB1和ZEB2。此外，lncRNA-ATB对骨肉瘤细胞增殖、迁移和侵袭以及骨肉瘤肿瘤生长的作用依赖于miR-200s的调控。综上所述，本研究表明lncRNA-ATB可能是骨肉瘤潜在的诊断和预后生物标志物及治疗靶点。
