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rs11671784基因的G/A多态性和rs895819基因的A/G多态性对中国人群胃癌易感性和miR-27a表达产生相反影响。

rs11671784 G/A and rs895819 A/G polymorphisms inversely affect gastric cancer susceptibility and miR-27a expression in a Chinese population.

作者信息

Song Bo, Yan Ge, Hao Hankun, Yang Bei

机构信息

Department of Gastroenterology, Yantai Shan Hospital, Yantai, Shangdong, China (mainland).

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland).

出版信息

Med Sci Monit. 2014 Nov 16;20:2318-26. doi: 10.12659/MSM.892499.

Abstract

BACKGROUND

rs895819 and rs11671784 are 2 SNPs in miR-27a that can influence the expression of mature miRNA. However, their role in gastric cancer development is still not well understood. This study aimed to determine whether these 2 polymorphisms are associated with gastric cancer risk in a Chinese population and how they influence the expression of miR-27a.

MATERIAL/METHODS: This was a case-control study and recruited 278 gastric cases and 278 healthy matched controls. Genotyping of these 2 SNPs among the participants were performed to assess their association with gastric cancer risk. Tumor samples from 59 patients who had physical resection were used for qRT-PCR analysis of miR-27a expression. To further valid the effects of these 2 SNPs, findings of previous studies were pooled to generate integrated evidence.

RESULTS

Individuals with rs895819 G variants exhibited significantly increased risk of gastric cancer, while subjects with rs11671784 A variants had significantly reduced gastric cancer risk. Among the patients, rs895819 G variants were moderately associated with lymphatic invasion and lymph node metastasis, while rs11671784 A variants were associated with significantly reduced risk of lymphatic invasion. qRT-PCR results demonstrated rs895819 polymorphism contributed to an aberrant process from pri-miR-27a to pre-miR-27a, but rs11671784 did not affect the transcription and post-transcription processes of the miR-27a gene. The subsequent meta-analysis largely confirmed the effects of these 2 SNPs on gastric cancer risk.

CONCLUSIONS

rs895819 and rs11671784 inversely affect gastric cancer risk and the influence was closely related to their effects on miR-27a expression.

摘要

背景

rs895819和rs11671784是miR-27a中的两个单核苷酸多态性(SNP),可影响成熟微小RNA(miRNA)的表达。然而,它们在胃癌发生中的作用仍未完全明确。本研究旨在确定这两个多态性是否与中国人群的胃癌风险相关,以及它们如何影响miR-27a的表达。

材料/方法:这是一项病例对照研究,招募了278例胃癌患者和278例健康匹配对照。对参与者进行这两个SNP的基因分型,以评估它们与胃癌风险的关联。对59例行手术切除患者的肿瘤样本进行miR-27a表达的定量逆转录聚合酶链反应(qRT-PCR)分析。为进一步验证这两个SNP的作用,汇总先前研究的结果以生成综合证据。

结果

携带rs895819 G变异的个体患胃癌的风险显著增加,而携带rs11671784 A变异的个体患胃癌的风险显著降低。在患者中,rs895819 G变异与淋巴管侵犯和淋巴结转移中度相关,而rs11671784 A变异与淋巴管侵犯风险显著降低相关。qRT-PCR结果表明,rs895819多态性导致从初级miR-27a(pri-miR-27a)到前体miR-27a(pre-miR-27a)的异常过程,但rs11671784不影响miR-27a基因的转录和转录后过程。随后的荟萃分析在很大程度上证实了这两个SNP对胃癌风险的影响。

结论

rs895819和rs11671784对胃癌风险的影响相反,且这种影响与其对miR-27a表达的作用密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18df/4245106/d84e71105098/medscimonit-20-2318-g001.jpg

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