Raymond Wai-Ming Lung and Xingyan Wang contributed equally to this work.
Article first published online: 18 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
How to Cite
Lung, R. W.-M., Wang, X., Tong, J. H.-M., Chau, S.-L., Lau, K.-M., Cheng, S.-H., Woo, J. K.-S., Woo, J., Leung, P.-C., Ng, M. H.-L., Tang, N. L.-S. and To, K.-F. (2012), A single nucleotide polymorphism in microRNA-146a is associated with the risk for nasopharyngeal carcinoma. Mol. Carcinog.. doi: 10.1002/mc.21937
No potential conflicts of interest were disclosed.
- Article first published online: 18 JUN 2012
- Manuscript Accepted: 30 MAY 2012
- Manuscript Revised: 5 APR 2012
- Manuscript Received: 20 JAN 2012
- nasopharyngeal carcinoma;
- genetic association;
- Argonaute2 co-immunoprecipitation
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.