LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2.
LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2.
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DOI：
10.1186/s12967-016-1100-9
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发表时间：
2016-12-20
影响因子：
7.4
通讯作者：
Samaniego F
中科院分区：
文献类型：
--
作者：
Wang X;Sehgal L;Jain N;Khashab T;Mathur R;Samaniego F
套细胞淋巴瘤（MCL）被认为是非霍奇金淋巴瘤的一种侵袭性亚型，具有可变的治疗反应。目前迫切需要确定新的标记物与预后和治疗价值的MCL。长链非编码RNA（lncRNA）已成为癌症（包括MCL）的关键调控因子。转移相关肺腺癌转录本1（MALAT 1），位于MCL的t（11; 14）特异性易位位点的lncRNA。已知MALAT 1在实体瘤和血液恶性肿瘤中过表达。然而，MALAT 1在MCL中的病理作用和临床相关性尚未完全了解。我们通过定量真实的时间聚合酶链反应（qRT-PCR）定量MCL样品（40）和CD 19 + B细胞中的MALAT 1，并将水平与临床结果相关联。我们沉默了MCL细胞系中的MALAT 1，并在致瘤试验中分析了细胞和转录复合物的形成。我们发现，与正常对照相比，MALAT 1在人类MCL肿瘤和细胞系中的表达升高，并且MALAT 1水平升高与较高的MCL国际预后指数（MIPI）和降低的总生存率相关。MCL与敲低MALAT 1显示受损的细胞增殖，促进细胞凋亡，并产生较少的克隆形成灶。在MALAT 1敲除后，p21和p27的表达增加受到zeste同源物增强子2（EZH 2）的调节。此外，在T350处EZH 2的磷酸化减少减弱了与MALAT 1的结合。我们的研究结果阐明了MALAT 1的致癌作用，它可能作为一种新的生物标志物和MCL的治疗靶点。本文的在线版本（doi：10.1186/s12967-016-1100-9）包含补充材料，可供授权用户使用。
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. 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. 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. Our findings illuminate the oncogenic role of MALAT1, which may serve as a novel biomarker and as a therapeutic target in MCL. The online version of this article (doi:10.1186/s12967-016-1100-9) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Ding L;Chen S;Liu P;Pan Y;Zhong J;Regan KM;Wang L;Yu C;Rizzardi A;Cheng L;Zhang J;Schmechel SC;Cheville JC;Van Deursen J;Tindall DJ;Huang H
通讯作者：
Huang H
影响因子：
11.5
作者：
Fan, Yu;Shen, Bing;Liu, Yong
通讯作者：
Liu, Yong
影响因子：
10.5
作者：
Kaneko, Syuzo;Li, Gang;Reinberg, Danny
通讯作者：
Reinberg, Danny
影响因子：
20.3
作者：
Chiarle, R;Budel, LM;Inghirami, G
通讯作者：
Inghirami, G
影响因子：
64.8
作者：
Margueron, Raphael;Reinberg, Danny
通讯作者：
Reinberg, Danny