ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma.

// Ren-Hui Chen 1, * , Yong Du 2, * , Ping Han 1 , Hong-Bo Wang 2 , Fa-Ya Liang 1 , Guo-Kai Feng 2 , Ai-Jun Zhou 2 , Mu-Yan Cai 3 , Qian Zhong 2 , Mu-Sheng Zeng 2 , Xiao-Ming Huang 1 1 Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China 2 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China 3 Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China * These authors have contributed equally to this work Correspondence to: Xiao-Ming Huang, e-mail: hxming@mail.sysu.edu.cn Mu-Sheng Zeng, e-mail: zengmsh@sysucc.org.cn Keywords: interferon-stimulated gene 15, nasopharyngeal carcinoma, prognosis, cancer stem cell Received: October 09, 2015      Accepted: February 06, 2016      Published: February 23, 2016 ABSTRACT 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.