Li Dandan, Zhang Hongchuang, Ma Lan, Han Yue, Xu Min, Wang Zhendong, Jiang Hongbing, Zhang Weibing, Wang Lin, Pan Yongchu
Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Sci Rep. 2016 Aug 11;6:31054. doi: 10.1038/srep31054.
We hypothesized that microRNA binding site single nucleotide polymorphisms (SNPs) in fibroblast growth factors (FGFs) and their receptor genes (FGFRs) may affect microRNA and mRNA interactions and are thereby associated with susceptibility of non-syndromic orofacial cleft (NSOC). Ten SNPs among the FGF and FGFR genes were selected and their associations with NSOC susceptibility were investigated in a case-control study of 602 patients with NSOC and 605 healthy controls. FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 showed suggestive association with NSOC susceptibility. In the combination analysis, the observed odds ratios (ORs) decreased with the number of protective alleles (rs1048201-T, rs3733336-G and rs546782-T) but were not statistically significant beyond the first comparison. Hsa-miRNA-496, hsa-miRNA-145 and hsa-miRNA-187 were predicted to be miRNAs with binding sites within/near these SNPs and were expressed in lip tissues. Decreased FGF2, FGF5 and FGF9 expression was observed in three cell lines transfected with the corresponding miRNAs. Moreover, the three SNPs could contribute to differential binding efficacy between hsa-miRNA-496 and FGF2, hsa-miRNA-145 and FGF5, hsa-miRNA-187 and FGF9 in luciferase assay. The results suggest that FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 are associated with the risk of NSOC and that these miRNA-FGF interactions may affect NSOC development.
我们推测，成纤维细胞生长因子（FGFs）及其受体基因（FGFRs）中的微小RNA结合位点单核苷酸多态性（SNPs）可能影响微小RNA与信使核糖核酸（mRNA）的相互作用，从而与非综合征性口腔颌面部裂隙（NSOC）的易感性相关。我们选择了FGF和FGFR基因中的10个SNP，并在一项包含602例NSOC患者和605例健康对照的病例对照研究中，调查了它们与NSOC易感性的关联。FGF2/rs1048201、FGF5/rs3733336和FGF9/rs546782显示出与NSOC易感性存在提示性关联。在联合分析中，观察到的比值比（ORs）随着保护性等位基因（rs1048201-T、rs3733336-G和rs546782-T）数量的增加而降低，但在首次比较之后差异无统计学意义。预测hsa-微小RNA-496、hsa-微小RNA-145和hsa-微小RNA-187是在这些SNP内部或附近具有结合位点的微小RNA，并在唇部组织中表达。在用相应微小RNA转染的三种细胞系中观察到FGF2、FGF5和FGF9表达降低。此外，在荧光素酶测定中，这三个SNP可能导致hsa-微小RNA-496与FGF2、hsa-微小RNA-145与FGF5、hsa-微小RNA-187与FGF9之间的结合效率存在差异。结果表明，FGF2/rs1048201、FGF5/rs3733336和FGF9/rs546782与NSOC风险相关，并且这些微小RNA-FGF相互作用可能影响NSOC的发育。
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