title: ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma.
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.
authors.affiliation: 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.
authors.forename: Ren-Hui
authors.initials: RH
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Fa-Ya
authors.initials: FY
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Guo-Kai
authors.initials: GK
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000401:mortality / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D014452:Ubiquitins; C074034:ISG15 protein, human
keywords: cancer stem cell; interferon-stimulated gene 15; nasopharyngeal carcinoma; prognosis