LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2

Journal of Translational Medicine

Research

Xin Wang¹  Neeraj Jain²  Rohit Mathur²  Lalit Sehgal²  Felipe Samaniego²  Tamer Khashab³ 

[1] Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA;Department of Internal Medicine, Lankenau Medical Center, Wynnewood, PA, USA;

关键词: Long non-coding RNA;    MALAT1;    MCL;    Cell cycle;    EZH2;    Phosphorylation;   

DOI  :  10.1186/s12967-016-1100-9

 received in 2016-07-27, accepted in 2016-11-29,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMantle cell lymphoma (MCL) is considered an aggressive subtype of non-Hodgkin’s lymphoma with variable treatment responses. There is an urgent need to identify novel markers with prognostic and therapeutic value for MCL. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancers, including MCL. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a lncRNA located at pathognomonic translocation site of t (11; 14) of MCL. MALAT1 is known to be overexpressed in solid tumors and hematologic malignancies. However, the pathological role and clinical relevance of MALAT1 in MCL are not completely understood.MethodsWe quantified MALAT1 in MCL samples (40) and CD19+ B cells by quantitative real time polymerase chain reaction (qRT-PCR) and correlated levels with clinical outcome. We silenced MALAT1 in MCL cell lines and analyzed cells in tumorigenic assays and formation of transcription complexes.ResultsWe found that the expression of MALAT1 was elevated in human MCL tumors and cell lines as compared to normal controls, and the elevated levels of MALAT1 correlated with higher MCL international prognostic index (MIPI) and reduced overall survival. MCL with knockdown of MALAT1 showed impaired cell proliferation, facilitated apoptosis and produced fewer clonogenic foci. The increased expression of p21 and p27 upon MALAT1 knockdown was regulated by enhancer of zeste homolog 2 (EZH2). Moreover, decreased phosphorylation of EZH2 at T350 attenuated the binding to MALAT1.ConclusionsOur findings illuminate the oncogenic role of MALAT1, which may serve as a novel biomarker and as a therapeutic target in MCL.

【 授权许可】

CC BY   
© The Author(s) 2016