CANT1 lncRNA Triggers Efficient Therapeutic Efficacy by Correcting Aberrant lncing Cascade in Malignant Uveal Melanoma
CANT1 lncRNA Triggers Efficient Therapeutic Efficacy by Correcting Aberrant lncing Cascade in Malignant Uveal Melanoma
复制标题
CANT1 lncRNA 通过纠正恶性葡萄膜黑色素瘤中的异常 lncRNA 触发有效的治疗效果
DOI：
10.1016/j.ymthe.2017.02.016
复制
发表时间：
2017-05-03
影响因子：
12.4
通讯作者：
Fan, Xianqun
中科院分区：
文献类型：
--
作者：
Xing, Yue;Wen, Xuyang;Fan, Xianqun
葡萄膜黑色素瘤是一种高死亡率的眼内恶性肿瘤。最近的研究已经显示了长链非编码RNA（lncRNA）在肿瘤发生中的功能;因此，靶向肿瘤特异性lncRNA异常已经成为开发治疗葡萄膜黑色素瘤的疗法的有吸引力的方法。在这项研究中，我们确定了一种新的核CANT 1 lncRNA（CASC 15-New-Transcript 1），它是一种必要的UM抑制因子。CANT 1显著降低了细胞培养物或携带肿瘤异种移植物的动物中的肿瘤转移能力和肿瘤形成。有趣的是，XIST lncRNA作为CANT 1的潜在靶点，JPX或FTX lncRNA随后作为背景铰链激活UM中的新CANT 1-JPX/FTX-XIST长非编码（lncing）途径。此外，CANT 1通过直接结合其启动子并促进H3 K4甲基化来触发JPX和FTX的表达。这些观察描绘了一种新的lncRNA级联反应，其中lncRNA直接建立一个lncing级联反应，而不需要编码基因，其目的是调节UM肿瘤发生，从而通过纠正葡萄膜黑色素瘤中的异常lncing级联反应，指定了一种新的“lncing级联反应更新”抗肿瘤治疗策略。
Uveal melanoma (UM) is an intraocular malignant tumor with a high mortality rate. Recent studies have shown the functions of long non-coding RNAs (lncRNAs) in tumorigenesis; thus, targeting tumor-specific lncRNA abnormalities has become an attractive approach for developing therapeutics to treat uveal melanoma. In this study, we identified a novel nuclear CANT1 lncRNA (CASC15-New-Transcript 1) that acts as a necessary UM suppressor. CANT1 significantly reduced tumor metastatic capacity and tumor formation, either in cell culture or in animals harboring tumor xenograft. Intriguingly, XIST lncRNA serves as a potential target of CANT1, and JPX or FTX lncRNA subsequently serves as a contextual hinge to activate a novel CANT1-JPX/FTX-XIST long non-coding (lncing) pathway in UM. Moreover, CANT1 triggers the expression of JPX and FTX by directly binding to their promoters and promoting H3K4 methylation. These observations delineate a novel lncing cascade in which lncRNAs directly build a lncing cascade without coding genes that aims to modulate UM tumorigenesis, thereby specifying a novel "lncing-cascade renewal" anti-tumor therapeutic strategy by correcting aberrant lncing cascade in uveal melanoma.