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长链非编码RNA ATB通过抑制miR-200s促进骨肉瘤细胞增殖、迁移和侵袭。

Long noncoding RNA ATB promotes osteosarcoma cell proliferation, migration and invasion by suppressing miR-200s.

作者信息

Han Feng, Wang Changhe, Wang Yi, Zhang Liang

机构信息

Department of Orthopedics, First People' Hospital of ShangqiuShangqiu 476100, Henan, China.

Department of Radiology, Zhumadian Central HospitalZhumadian 463000, Henan, China.

出版信息

Am J Cancer Res. 2017 Apr 1;7(4):770-783. eCollection 2017.

Abstract

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.

摘要

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。

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