Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
PLoS One. 2012;7(10):e47544. doi: 10.1371/journal.pone.0047544. Epub 2012 Oct 11.
MicroRNAs (miRNAs) have been reported to play a key role in oncogenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the miRNA-mRNA interactions, hence promoting tumorigenesis. In the present study, we hypothesized that potentially functional polymorphisms in miRNA processing genes may contribute to head and neck cancer (HNC) susceptibility. To test this hypothesis, we genotyped three SNPs at miRNA binding sites of miRNA processing genes (rs1057035 in 3'UTR of DICER, rs3803012 in 3'UTR of RAN and rs10773771 in 3'UTR of HIWI) with a case-control study including 397 HNC cases and 900 controls matched by age and sex in Chinese. Although none of three SNPs was significantly associated with overall risk of HNC, rs1057035 in 3'UTR of DICER was associated with a significantly decreased risk of oral cancer (TC/CC vs. TT: adjusted OR = 0.65, 95% CI = 0.46-0.92). Furthermore, luciferase activity assay showed that rs1057035 variant C allele led to significantly lower expression levels as compared to the T allele, which may be due to the relatively high inhibition of hsa-miR-574-3p on DICER mRNA. These findings indicated that rs1057035 located at 3'UTR of DICER may contribute to the risk of oral cancer by affecting the binding of miRNAs to DICER. Large-scale and well-designed studies are warranted to validate our findings.
微小 RNA（miRNAs）已被报道在肿瘤发生中发挥关键作用。miRNA 加工基因和 miRNA 结合位点的遗传变异可能影响 miRNA 的生物发生和 miRNA-mRNA 相互作用，从而促进肿瘤发生。在本研究中，我们假设 miRNA 加工基因中潜在的功能性多态性可能导致头颈部癌症（HNC）易感性。为了验证这一假设，我们使用病例对照研究，对 miRNA 加工基因（DICER 3'UTR 中的 rs1057035、RAN 3'UTR 中的 rs3803012 和 HIWI 3'UTR 中的 rs10773771）的三个 SNP 进行了基因分型，该研究包括 397 例 HNC 病例和 900 例年龄和性别匹配的对照。虽然这三个 SNP 均与 HNC 的总体风险无显著相关性，但 DICER 3'UTR 中的 rs1057035 与口腔癌的风险显著降低相关（TC/CC 与 TT：调整后的 OR=0.65，95%CI=0.46-0.92）。此外，荧光素酶活性测定表明，与 T 等位基因相比，rs1057035 变体 C 等位基因导致表达水平显著降低，这可能是由于 hsa-miR-574-3p 对 DICER mRNA 的相对高抑制。这些发现表明，位于 DICER 3'UTR 的 rs1057035 可能通过影响 miRNA 与 DICER 的结合而导致口腔癌的风险。需要进行大规模和精心设计的研究来验证我们的发现。
