ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma.
ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma.
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ISG15预测鼻咽癌不良预后并促进癌症干细胞表型
DOI：
10.18632/oncotarget.7626
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发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Huang XM
中科院分区：
文献类型：
--
作者：
Chen RH;Du Y;Han P;Wang HB;Liang FY;Feng GK;Zhou AJ;Cai MY;Zhong Q;Zeng MS;Huang XM
干扰素刺激基因15（Interferon-stimulated gene 15，ISG15）是第一个被发现的泛素样蛋白，以其抗病毒能力而闻名。然而，其在肿瘤发生中的作用仍然存在争议。在这里，使用RNA-seq分析，我们确定ISG15作为鼻咽癌（NPC）中的差异表达基因，并验证其在NPC样品和细胞中的过表达。鼻咽癌组织中高水平的ISG15与更频繁的局部复发和更短的总生存期和无病生存期相关。ISG15过表达促进NPC细胞中的癌症干细胞表型，包括增加的集落和肿瘤球形成能力、多能性相关基因表达和体内致瘤性。相比之下，ISG15的敲低减弱了NPC细胞中的干性特征。此外，ISG15的过表达增加了鼻咽癌细胞对放射和顺铂（DDP）治疗的抵抗。我们的研究证实了ISG15的促肿瘤作用，并表明ISG15是NPC的预后预测因子和潜在的治疗靶点。
Interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, is known for its anti-viral capacity. However, its role in tumorigenesis remains controversial. Here, using RNA-seq profiling analysis, we identified ISG15 as a differentially expressed gene in nasopharyngeal carcinoma (NPC) and validated its overexpression in NPC samples and cells. High ISG15 levels in NPC tissues were correlated with more frequent local recurrence and shorter overall survival and disease-free survival. ISG15 overexpression promoted a cancer stem cell phenotype in NPC cells, including increased colony and tumorsphere formation abilities, pluripotency-associated genes expression, and in vivo tumorigenicity. By contrast, knockdown of ISG15 attenuated stemness characteristics in NPC cells. Furthermore, overexpression of ISG15 increased NPC cell resistance to radiation and cisplatin (DDP) treatment. Our study demonstrates a protumor role of ISG15, and suggests that ISG15 is a prognostic predictor and a potential therapeutic target for NPC.