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首页 > 医学词汇大全 > Euchromatic histone-lysine N-methyltransferase 2
Euchromatic histone-lysine N-methyltransferase 2

肾内泌尿

关键词肾内泌尿 临床研究术语 常染色质组蛋白赖氨酸N-甲基转移酶2

词汇介绍

拓展阅读

解析

Euchromatic  /,ju:krəu'mætik/

释    义   adj. 常染色质的

例    句   Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods.许多剩余的常染色质gap与重复有关,需要用新方法专门研究。

 

Histone  英  /'hɪstəʊn/  美  /'hɪston/

释    义   n. [生化] 组蛋白

例    句   The enzymes in question are histone acetyltransferase (which adds acetyl groups to proteins) and methylated DNA-binding protein-2 (which removes methyl groups from DNA).这两种酶是组蛋白乙酰转移酶(它能给蛋白质添加乙酰基)和甲基化DNA结合蛋白- 2(它能把DNA上的甲基去除)。

 

Lysine  英  /'laɪsiːn/  美  /'laɪsɪn/

释    义   n. [生化] 赖氨酸

例    句   Corynebacterium glutamicum high-serine is used as a lysine-deficient strain of the bacteria fermentation in the industry.谷氨酸棒杆菌高丝氨酸在工业上用作细菌发酵的赖氨酸缺乏菌株。

 

Methyltransferase  /,meθil'trænsfəreis/

释    义   n. [生化] 甲基转移酶

例    句   Conclusion: The results suggest that SET07 functions as a histone methyltransferase which plays an important role in the life cycle of cells and carcinogenesis.结论:上述结果提示SET07基因可能具有甲基转移酶的功能,在调节细胞生长周期、控制肿瘤的发生发展中发挥重要作用。

概述

  该基因的中英文全称:常染色质组蛋白赖氨酸N甲基转移酶2,简写为EHMT2,又被称为G9A、BAT8、GAT8、NG36、KMT1C、C6orf30。亚细胞定位在细胞核。该基因编码一个甲基化转移酶蛋白,对组蛋白H3的赖氨酸残基进行甲基化。该蛋白在组蛋白H3第9位的赖氨酸的甲基化导致招募表观遗传调控因子,最终导致转录抑制。最初研究认为该基因是由NG36和G9a这两个基因。其通过可变剪切可以产生很多转录本。其在卵巢、睾丸等25个组织中均有表达。其在染色体上的位置是6

Inhibition of a G9a/DNMT Network Triggers Immune-Mediated Bladder Cancer Regression复制标题

抑制G9a/DNMT网络触发免疫介导的膀胱癌消退

发表时间:2019-07-25

影响因子:36.1

作者: Segovia C

期刊:Nat Med

Bladder cancer is lethal in its advanced, muscle-invasive phase with very limited therapeutic advances. Recent molecular characterization has defined new (epi)genetic drivers and potential targets for bladder cancer. The immune checkpoint inhibitors have shown remarkable efficacy but only in a limited fraction of bladder cancer patients. Here, we show that high G9a (EHMT2) expression is associated with poor clinical outcome in bladder cancer and that targeting G9a/DNMT methyltransferase activity with a novel inhibitor (CM-272) induces apoptosis and immunogenic cell death. Using an immunocompetent quadruple-knockout (PtenloxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Rbl1-/-) transgenic mouse model of aggressive metastatic, muscle-invasive bladder cancer, we demonstrate that CM-272 + cisplatin treatment results in statistically significant regression of established tumors and metastases. The antitumor effect is significantly improved when CM-272 is combined with anti-programmed cell death ligand 1, even in the absence of cisplatin. These effects are associated with an endogenous antitumor immune response and immunogenic cell death with the conversion of a cold immune tumor into a hot tumor. Finally, increased G9a expression was associated with resistance to programmed cell death protein 1 inhibition in a cohort of patients with bladder cancer.

译文

膀胱癌是致命的,在它的晚期,肌肉侵袭期,治疗进展非常有限。最近的分子特性研究确定了新的(epi)基因驱动和膀胱癌的潜在靶点。免疫检查点抑制剂显示了显著的效果,但只在有限的部分膀胱癌患者。在本研究中,我们发现膀胱癌中G9a (EHMT2)的高表达与较差的临床结果相关,并且使用新型抑制剂(CM-272)靶向G9a/DNMT甲基转移酶活性可诱导细胞凋亡和免疫原性细胞死亡。采用免疫活性四基因敲除(PtenloxP/loxP;Trp53loxP / loxP;Rb1loxP / loxP;Rbl1-/-转基因小鼠模型侵袭性转移,肌肉浸润性膀胱癌,我们证明,CM-272 +顺铂治疗导致建立的肿瘤和转移有统计学意义的回归。CM-272联合抗程序性细胞死亡配体1,即使在没有顺铂的情况下,其抗肿瘤效果也明显提高。这些作用与内源性抗肿瘤免疫反应和免疫原性细胞死亡有关,这些免疫原性细胞死亡与免疫冷瘤转化为热瘤有关。最后,在一组膀胱癌患者中,G9a表达的增加与对程序性细胞死亡蛋白1抑制的抵抗有关。