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A single nucleotide polymorphism in microRNA-146a is associated with the risk for nasopharyngeal carcinoma

Authors

  • Raymond Wai-Ming Lung,

    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Xingyan Wang,

    1. Department of Chemical Pathology, Laboratory of Genetics of Disease Susceptibility at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
    2. Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Joanna Hung-Man Tong,

    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Shuk-Ling Chau,

    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Kin-Mang Lau,

    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Shuk-Hang Cheng,

    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • John Kong-Sang Woo,

    1. Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
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  • Jean Woo,

    1. Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Ping-Chung Leung,

    1. Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
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  • Margaret Heung-Ling Ng,

    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Nelson Leung-Sang Tang,

    Corresponding author
    1. Department of Chemical Pathology, Laboratory of Genetics of Disease Susceptibility at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
    2. Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
    • Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

      Department of Chemical Pathology, Laboratory of Genetics of Disease Susceptibility at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

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  • Ka-Fai To

    Corresponding author
    1. Department of Anatomical and Cellular Pathology at Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Center for Cancer, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China
    2. Institute of Digestive Disease at Li Ka-Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
    • Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

      Department of Chemical Pathology, Laboratory of Genetics of Disease Susceptibility at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

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  • Raymond Wai-Ming Lung and Xingyan Wang contributed equally to this work.
  • No potential conflicts of interest were disclosed.

Abstract

A common GC polymorphism within miRNA-146a precursor region (rs2910164) has been associated with the risk of various cancers despite the underlying mechanism is unclear. In the current study, we aimed to examine the role of rs2910164 in the pathogenesis and predisposition to nasopharyngeal carcinoma (NPC). The GC polymorphism in 233 NPC patients, 173 matched controls and 3613 healthy elderly subjects in our locality were first determined using melting temperature (Tm)-shift allele-specific genotyping method. Results in our case–control study indicated that CC genotype was associated with the risk effect of NPC (adjusted odds ratio of GC + GG vs. CC, 0.49; 95% confidence interval, 0.35–0.69; P < 0.0001). Using real-time polymerase chain reaction (PCR) assay, we subsequently revealed that expressions of both miR-146a and its passenger strand (miR-146a*C or miR-146a*G) were increased in NPC samples (P < 0.001), albeit expression of miR-146a was not linked to the genotype. Furthermore, miR-146a*C in NPC was significantly increased in CC genotype (CC vs. GC, P = 0.038). Finally, we demonstrated by co-immunoprecipitation and luciferase reporter assays that all three miR-146a precursor-derived mature miRNAs interacted with Argonaute2 (Ago2) protein complex and could function as gene silencers. Taken together, our results showed that the variant C in rs2910164 was associated with the predisposition of NPC in Chinese population. This polymorphism may influence the risk of NPC by producing active mature miR-146a*C that regulate distinct set of target genes. These findings may enrich our understanding of how miRNA single nucleotide polymorphism affect NPC pathogenesis, and may have potential implications to improve NPC treatment in the future. © 2012 Wiley Periodicals, Inc.

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