长链非编码RNA TUG1在骨肉瘤中的发生机制—系统回顾和荟萃分析

目的本研究旨在系统回顾长链非编码RNA TUG1（lncRNA TUG1）在骨肉瘤发生、发展中的机制，以及探讨TUG1在评估骨肉瘤患者预后中的价值。 方法系统检索PubMed、Embase、Web of Science、CochraneLibrary、中国知网（CNKI）和万方医学数据库，收集TUG1与骨肉瘤发生及预后的相关文献。系统回顾TUG1在骨肉瘤发生、发展中的机制，并采用Stata12软件（Stata公司，美国）对TUG1与骨肉瘤患者预后的相关性进行meta分析。 结果目前的研究表明，TUG1主要通过发挥竞争性内源RNA（competing endogenous RNA）效应调控骨肉瘤细胞增殖、凋亡和侵袭等过程，涉及通路包括AKT信号通路和Wnt/β-catenin信号通路。本研究共纳入4篇文献进行meta分析，共244例骨肉瘤患者。TUG1表达升高的骨肉瘤患者总体生存率低于TUG1表达降低的骨肉瘤患者（OR=1.921，95% CI：1.361，2.712，P=0.000）。不仅如此，骨肉瘤患者组织中TUG1表达升高往往提示肿瘤具有更大的体积（OR=4.084，95% CI：2.313，7.211，P=0.000）、较高的临床分级（OR=0.247，95% CI：0.133，0.539，P=0.000）和更早期远处转移（OR=1.943，95% CI：1.130，3.339，P=0.016）。然而，其与患者性别（OR=1.055，95% CI：0.620，1.793，P=0.844）和肿瘤发生部位（OR=0.806，95% CI：0.424，1.530，P=0.509）无显著相关性。 结论长链非编码RNATUG1与骨肉瘤发生、发展密切相关。不仅如此，TUG1表达升高提示骨肉瘤患者不良临床预后，其可能是一种评估骨肉瘤患者预后的生物学标志物。

The role and prognostic value of long noncoding RNA TUG1 in human osteosarcoma: A systematic review and meta-analysis

ObjectiveThis study aimed toinvestigate the underlying mechanisms, and the prognostic value of long non coding RNA taurine-upregulated gene 1 (lncRNA, TUG1)inthe development and progression of osteosarcoma. MethodsPubMed, Embase, Web of Science, Cochrane Library, ChinaNational Knowledge Internet (CNKI) and Wanfang database were systematically searched for the relevant literature of TUG1 in the development and prognosis of osteosarcoma. STATA12 (Stata Corp, College Station, Texas) was used to estimate pooled effects and the heterogeneity among studies. ResultsCurrent studies indicated that TUG1 regulates the proliferation, apoptosis, and invasion by acting as a ceRNA. The underlying mechanisms include AKT and Wnt/β-catenin signal pathways. Four records with a total of 244 osteosarcoma patients were enrolled in this study. The pooled results showed that the patients with high TUG1 expression had shorter overall survival (OS) compared to the patients with low TUG1 expression (OR=1.921, 95% CI: 1.361, 2.712, P=0.000). Moreover, elevated TUG1 expression was associated with advanced tumor size (OR=4.084, 95% CI: 2.313, 7.211, P=0.000), clinical stage (OR=0.258, 95%CI: 0.098, 0.682, P=0.006), and early distant metastasis (OR=1.943, 95% CI: 1.130, 3.339, P=0.016). Nevertheless, high TUG1 expression was not related to gender (OR=1.055, 95% CI: 0.620, 1.793, P=0.844) and anatomical dislocation (OR=0.806, 95% CI: 0.424, 1.530, P=0.509). ConclusionsLncRNA TUG1 plays an important role in the molecular mechanisms of osteosarcoma. Elevated TUG1 expression indicates poor OS and clinical parameters in patients undergoing osteosarcoma, which may be used as a moderate prognostic biomarker in human osteosarcoma.