LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern
LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern
复制标题
LncRNA GClnc1 促进胃癌发生，并可作为 WDR5 和 KAT2A 复合物的模块化支架来指定组蛋白修饰模式
DOI：
10.1158/2159-8290.cd-15-0921
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发表时间：
2016-07-01
期刊：
影响因子：
28.2
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
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作者：
Sun, Tian-Tian;He, Jie;Fang, Jing-Yuan
长链非编码RNA（lncRNA）在肿瘤发生中起作用。然而，lncRNA在人类胃癌中的功能仍然很大程度上未知。在这项研究中，我们确定了一种新的lncRNA，GClnc1，这是上调和与肿瘤发生，肿瘤大小，转移，预后不良的胃癌。GClnc1在多种胃癌模型中影响胃癌细胞增殖、侵袭和转移。GClnc1结合WDR5（组蛋白甲基转移酶复合物的关键组分）和KAT2A组蛋白乙酰转移酶，作为WDR5和KAT2A复合物的模块支架，协调它们的定位，指定靶基因上的组蛋白修饰模式，包括SOD2，从而改变胃癌细胞生物学。因此，GClnc1在胃癌中是机制性、功能性和临床致癌性的。意义：本文报道了一种新的lncRNA，GClnc1，它可能作为一个支架募集WDR 5和KAT 2A复合物并修饰靶基因的转录。GClnc1是一种在人胃癌中具有致癌作用的lncRNA。(C)2016年AACR。
Long noncoding RNAs (lncRNA) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identified a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, GClnc1 bound WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase, acted as a modular scaffold of WDR5 and KAT2A complexes, coordinated their localization, specified the histone modification pattern on the target genes, including SOD2, and consequently altered gastric cancer cell biology. Thus, GClnc1 is mechanistically, functionally, and clinically oncogenic in gastric cancer. Targeting GClnc1 and its pathway may be meaningful for treating patients with gastric cancer.SIGNIFICANCE: This report documents a novel lncRNA, GClnc1, which may act as a scaffold to recruit the WDR5 and KAT2A complex and modify the transcription of target genes. This study reveals that GClnc1 is an oncogenic lncRNA in human gastric cancer. (C) 2016 AACR.