Ding Xia, Wang Xi, Lin Ming, Xing Yue, Ge Shengfang, Jia Renbing, Zhang He, Fan Xianqun, Li Jin
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China.
FEBS Lett. 2016 Jun;590(12):1729-38. doi: 10.1002/1873-3468.12220. Epub 2016 Jun 7.
Uveal melanoma (UM) is the most common primary intraocular tumour in adults and has a high incidence. Nearly 50% of patients with UM develop metastases after diagnosis. Long noncoding RNAs (lncRNAs) are involved in both oncogenic and tumour suppression pathways. We show that lncRNA PAUPAR is present at low levels in UM tissues and cell lines and modulates the tumourigenesis of UM in vitro and in vivo. The ectopic expression of PAUPAR in UM cells revealed that PAUPAR acts as a necessary UM suppressor and induces the silencing of HES1 expression, which significantly reduces tumour metastasis. Mechanistically, PAUPAR modulates HES1 expression by inhibiting histone H3K4 methylation. These data support a role of this lncRNA as a novel therapeutic target in cancer prevention and treatment.
葡萄膜黑色素瘤（UM）是成人中最常见的原发性眼内肿瘤，发病率很高。近50%的UM患者在诊断后会发生转移。长链非编码RNA（lncRNA）参与致癌和肿瘤抑制途径。我们发现lncRNA PAUPAR在UM组织和细胞系中低水平表达，并在体外和体内调节UM的肿瘤发生。PAUPAR在UM细胞中的异位表达表明，PAUPAR作为一种必要的UM抑制因子，可诱导HES1表达沉默，从而显著减少肿瘤转移。从机制上讲，PAUPAR通过抑制组蛋白H3K4甲基化来调节HES1表达。这些数据支持了这种lncRNA作为癌症预防和治疗新靶点的作用。
