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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2016

Open Access 01-12-2016 | Research

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

Authors: Xin Wang, Lalit Sehgal, Neeraj Jain, Tamer Khashab, Rohit Mathur, Felipe Samaniego

Published in: Journal of Translational Medicine | Issue 1/2016

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Abstract

Background

Mantle 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.

Methods

We 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.

Results

We 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.

Conclusions

Our findings illuminate the oncogenic role of MALAT1, which may serve as a novel biomarker and as a therapeutic target in MCL.
Appendix
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Metadata
Title
LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2
Authors
Xin Wang
Lalit Sehgal
Neeraj Jain
Tamer Khashab
Rohit Mathur
Felipe Samaniego
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2016
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-016-1100-9

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