MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.
MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.
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MALAT1预测骨肉瘤患者的生存率不佳，并通过与EZH2联合促进细胞转移。
DOI：
10.18632/oncotarget.16551
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Pan X
中科院分区：
文献类型：
--
作者：
Huo Y;Li Q;Wang X;Jiao X;Zheng J;Li Z;Pan X
骨肉瘤是最常见的骨癌类型，尤其是在儿童和年轻人中。最近，长链非编码RNA（lncRNA）已成为包括骨肉瘤在内的几种癌症的新的预后标志物和基因调控因子。在这项研究中，我们研究了lncRNA MALAT 1在骨肉瘤中的作用，特别关注其转录调控及其与EZH 2的相互作用。我们的研究结果表明，MALAT 1在骨肉瘤标本和细胞系中显着增加。ROC曲线分析显示MALAT 1的曲线下面积高于碱性磷酸酶，Kaplan-Meier生存分析显示血清MALAT 1水平高的患者生存率降低。敲低MALAT 1基因可降低骨肉瘤细胞的侵袭能力并促进E-cadherin的表达。机制研究表明，MALAT 1被TGF-β转录激活。此外，EZH 2在骨肉瘤中高表达并与lncRNA MALAT 1的3'端区域相关，并且这种相关最终抑制了E-cadherin的表达。随后，我们的获得和丧失功能测定显示MALAT 1过表达促进细胞转移并降低E-cadherin水平，然而，这种作用被EZH 2敲低部分逆转。总之，我们的工作阐明了lncRNA MALAT 1是骨肉瘤的潜在诊断和预后因子，并进一步证明了MALAT 1如何赋予致癌功能。因此，lncRNA MALAT 1可能作为骨肉瘤患者的一个有前途的预后和治疗靶点。
Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-β. Additionally, EZH2 is highly expressed and associated with the 3’ end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.
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