title: Argonaute 2 and nasopharyngeal carcinoma: a genetic association study and functional analysis.
abstract: BACKGROUND
  Argonaute 2 (AGO2), a central component of RNA-induced silencing complex, plays critical roles in cancer. We examined whether the single nucleotide polymorphisms (SNPs) of AGO2 were related to the risk of nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Twenty-five tag SNPs within AGO2 were genotyped in Guangxi population consisting of 855 NPC patients and 1036 controls. The SNPs significantly associated with NPC were further replicated in Guangdong population consisting of 996 NPC patients and 972 controls. Functional experiments were conducted to examine the biologic roles of AGO2 in NPC.
  
  
  RESULTS
  A significantly increased risk of advanced lymph node metastasis of NPC was identified for the AGO2 rs3928672 GA + AA genotype compared with GG genotype in both the Guangxi and Guangdong populations (combined odd ratio = 2.08, 95 % confidence interval = 1.44-3.01, P = 8.60 × 10(-5)). Moreover, the AGO2 protein expression levels of rs3928672 GA + AA genotype carriers were higher than the GG genotype carriers in the NPC tissues (P = 0.041), and AGO2 was significantly over-expressed in NPC tissues compared with non-cancerous nasopharyngeal tissues (P = 0.011). In addition, AGO2 knockdown reduced cell proliferation, induced apoptosis, and inhibited migration of NPC cells. Furthermore, gene expression microarray showed that genes altered following AGO2 knockdown were clustered in tumorigenesis and metastasis relevant pathways.
  
  
  CONCLUSIONS
  Our findings suggest that the genetic polymorphism in AGO2 may be a risk factor for the advanced lymph node metastasis of NPC in Chinese populations, and AGO2 acts as an oncogene in the development of NPC.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. lipeiyao214@gmail.com.
authors.forename: Peiyao
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. zb.meng@163.com.|Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Basic Medical Sciences, Beijing, P.R. China. zb.meng@163.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. zhaiyun2012@126.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. zhanghx08@126.com.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. yulixia_lili@163.com.
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. wangzhifu_1@163.com.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. babylovehopi@163.com.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. birchcpb@163.com.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. arhelion@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. hanyuqing_1985@163.com.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. y_zh2001@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Microbial Genomics, Beijing Institute of Biotechnology, Beijing, P.R. China. chenhp0909@163.com.
authors.forename: Huipeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of Microbial Genomics, Beijing Institute of Biotechnology, Beijing, P.R. China. lingny@me.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Laboratory of Microbial Genomics, Beijing Institute of Biotechnology, Beijing, P.R. China. liyuxia990306@126.com.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Affiliated Cancer Hospital of Guangxi Medical University, Nanning, P.R. China. 13907863066@139.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China. beijinx@mail.sysu.edu.cn.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China. zengyx@sysucc.org.cn.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. hefc@nic.bmi.ac.cn.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, No. 27, Taiping Road, Haidian District, Beijing, 100850, P.R. China. zhougq114@126.com.
authors.forename: Gangqiao
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mesh_terms: D000483:Alleles; D017209:Apoptosis; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002681:China / Q000453:epidemiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D055785:Gene Knockdown Techniques; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008207:Lymphatic Metastasis; D008297:Male; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012306:Risk
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins