Oncotarget

Research Papers:

MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2

Yanqing Huo, Qingbo Li, Xiqian Wang, Xiejia Jiao, Jiachun Zheng, Zhiqiang Li and Xiaohan Pan _

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Oncotarget. 2017; 8:46993-47006. https://doi.org/10.18632/oncotarget.16551

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Abstract

Yanqing Huo1, Qingbo Li1, Xiqian Wang1, Xiejia Jiao1, Jiachun Zheng1, Zhiqiang Li1 and Xiaohan Pan2

1Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China

2Department of Health Management, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China

Correspondence to:

Xiaohan Pan, email: xiaohanpan@163.com

Keywords: MALAT1, osteosarcoma, TGF-β, metastasis, EZH2

Received: January 25, 2017    Accepted: March 06, 2017    Published: March 24, 2017

ABSTRACT

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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