A Single Nucleotide Polymorphism in MicroRNA-146a Is Associated With the Risk for Nasopharyngeal Carcinoma
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AbstractA 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 (T-m)-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. (c) 2012 Wiley Periodicals, Inc.
All Author(s) ListLung RWM, Wang XY, Tong JHM, Chau SL, Lau KM, Cheng SH, Woo JKS, Woo J, Leung PC, Ng MHL, Tang NLS, To KF
Journal nameMolecular Carcinogenesis
Detailed description52 Suppl 1. doi: 10.1002/mc.21937. Epub 2012 Jun 18
Volume Number52
Pages28 - 38
LanguagesEnglish-United Kingdom
KeywordsArgonaute2 co-immunoprecipitation; genetic association; miR-146a*; nasopharyngeal carcinoma; rs2910164
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Oncology; ONCOLOGY

Last updated on 2021-14-09 at 00:21