miR-146a基因rs2910164 G/C多态性与miR-146a异常表达与胃癌风险相关性的研究

Association of miR-146a rs2910164 G/C polymorphism with its abnormal expression and risk of gastric cancer

目的探讨miR-146a基因单核苷酸多态位点rs2910164 G/C是否影响miR-146a的表达并改变其对胃癌的易感性。方法选取53例胃癌患者和6株胃癌细胞株(AGS、BGC-823、HGC27、MKN-28、MKN-45和SGC-7901),采用Taqman定量PCR检测miR-146a的表达,构建miR-146a过表达细胞模型,探究miR-146a过表达对胃癌细胞AGS生长的影响,然后对417例胃癌患者和420名无癌对照者进行病例对照研究,检测miR-146a基因rs2910164位点的等位基因和基因型频率,基因分型采用Taqman等位基因判别法;用Taqman对65例已知基因型胃癌患者的成熟和pri-miR-146a转录本进行定量分析。结果miR-146a在53例胃癌和6种胃癌细胞系中表达下调,miR-146a的过表达通过抑制AGS细胞G1/S期转变抑制胃癌细胞生长;病例对照研究结果显示,与GG基因型受试者相比,携带GC/CC基因型的受试者患胃癌的风险显著降低;与GG基因型相比,GC/CC基因型miR-146a G/C SNP显著提高成熟miR-146a水平。结论miR-146a的下调在胃癌发生中发挥重要作用,miR-146a基因rs2910164多态位点可通过影响成熟miR-146a的加工过程而降低胃癌风险。

Objective To assess the influence of rs2910164 G/C single nucleotide polymorphism(SNP)of the miR-146a gene on its expression and susceptibility to gastric cancer.Methods Fifty three gastric cancer patients and six gastric cancer cell lines were selected for determining the miR-146a expression by Taqman quantitative PCR.A model was constructed to assess the influence of miR-146a overexpression on the growth of AGS gastric cancer cells.A case-control study involving 417 gastric cancer patients and 420 cancer-free individuals was then conducted,and the allelic and genotypic frequencies of the rs2910164 G/C SNP were compared.The genotypes of all subjects were determined by using a Taqman allelic discrimination assay.A Taqman assay was also used to quantify mature and pri-miR-146a transcripts among 65 gastric cancer patients with known genotypes.Results The expression of miR-146a was down-regulated among the 53 gastric cancer patients and six gastric cancer cell lines.Over-expression of miR-146a has suppressed the growth of gastric cancer by inhibiting the G1/S-phase transition of AGS cells.The case-control study showed that subjects with GC/CC genotypes had significantly lower risk for gastric cancer compared with those with GG genotype.In addition,miR-146a G/C SNP has significantly increased the level of mature miR-146a in those with GC/CC genotype compared with GG genotype.Conclusion Down-regulation of miR-146a may play an important role in the pathogenesis of gastric cancer.The rs2910164 polymorphism of the miR-146a gene may reduce the risk of gastric cancer by influencing the processing of mature miR-146a.