PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma.
PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma.
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PRMT2 将组蛋白 H3R8 不对称二甲基化与胶质母细胞瘤的致癌激活和肿瘤发生联系起来。
DOI：
10.1038/s41467-018-06968-7
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发表时间：
2018-10-31
影响因子：
16.6
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Dong F;Li Q;Yang C;Huo D;Wang X;Ai C;Kong Y;Sun X;Wang W;Zhou Y;Liu X;Li W;Gao W;Liu W;Kang C;Wu X
转录失调在多形性胶质母细胞瘤（GBM）中起着至关重要的作用。因此，鉴定致癌转录程序所必需的表观遗传修饰剂是设计有效治疗这种致命疾病的关键。在这里，我们报告蛋白精氨酸甲基转移酶2（PRMT2）在GBM中高度表达，并与预后不良相关。PRMT2的沉默或失活在体外抑制GBM细胞生长和胶质母细胞瘤干细胞自我更新，并抑制原位肿瘤生长，伴随着主要与癌症中的细胞周期进展和途径相关的基因的显著失调。PRMT2在机制上负责H3R8不对称甲基化（H3R8me2a），其在启动子和增强子处的富集与已知的活性组蛋白标记密切相关，并且是维持靶基因表达所需的。总之，这项研究表明，PRMT2作为一个转录共激活基因的表达程序在GBM发病机制，并提供了一个基本原理PRMT2靶向侵袭性胶质瘤。蛋白质精氨酸甲基转移酶（PRMT）在癌症表观遗传调控中的作用仍然知之甚少。在这里，作者表明PRMT2在多形性胶质母细胞瘤（GBM）中高度表达，并提供了PRMT2在GBM发病机制中作为致癌基因表达程序的转录共激活因子的证据，至少部分依赖于其H3R8me2a活性。
Transcriptional deregulation has a vital role in glioblastoma multiforme (GBM). Thus, identification of epigenetic modifiers essential for oncogenic transcriptional programs is a key to designing effective therapeutics for this deadly disease. Here we report that Protein Arginine Methyltransferase 2 (PRMT2) is highly expressed in GBM and correlated with poor prognosis. The silencing or inactivation of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro, and suppresses orthotopic tumor growth, accompanied with significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. Mechanistically PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a), whose enrichment at promoters and enhancers is closely correlated with known active histone marks and is required for the maintenance of target gene expression. Together, this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas. The role of protein arginine methyltransferases (PRMTs) in epigenetic regulation in cancer is still poorly understood. Here, the authors show that PRMT2 is highly expressed in Glioblastoma multiforme (GBM) and provide evidence that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs, at least partly dependent on its H3R8me2a activity, in GBM pathogenesis.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
14.9
作者：
Girardot M;Hirasawa R;Kacem S;Fritsch L;Pontis J;Kota SK;Filipponi D;Fabbrizio E;Sardet C;Lohmann F;Kadam S;Ait-Si-Ali S;Feil R
通讯作者：
Feil R
272 例胶质瘤的 RNA 测序揭示了继发性胶质母细胞瘤中一种新的、复发性 PTPRZ1-MET 融合转录本。
影响因子：
7
作者：
Bao ZS;Chen HM;Yang MY;Zhang CB;Yu K;Ye WL;Hu BQ;Yan W;Zhang W;Akers J;Ramakrishnan V;Li J;Carter B;Liu YW;Hu HM;Wang Z;Li MY;Yao K;Qiu XG;Kang CS;You YP;Fan XL;Song WS;Li RQ;Su XD;Chen CC;Jiang T
通讯作者：
Jiang T
影响因子：
4
作者：
Eram MS;Shen Y;Szewczyk M;Wu H;Senisterra G;Li F;Butler KV;Kaniskan HÜ;Speed BA;Dela Seña C;Dong A;Zeng H;Schapira M;Brown PJ;Arrowsmith CH;Barsyte-Lovejoy D;Liu J;Vedadi M;Jin J
通讯作者：
Jin J
影响因子：
11.8
作者：
Blythe, Shelby A.;Cha, Sang-Wook;Tadjuidje, Emmanuel;Heasman, Janet;Klein, Peter S.
通讯作者：
Klein, Peter S.