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原发性微小RNA-34b/c启动子区基因变异与胶质瘤风险的关联

Association Between Genetic Variant in the Promoter of Pri-miR-34b/c and Risk of Glioma.

作者信息

Li Jinghui, Liu Xiaoyu, Qiao Yu, Qi Renli, Liu Shunjin, Guo Jing, Gui Yang, Li Juanjuan, Yu Hualin

机构信息

Department of Anatomy & Histology and Embryology, Kunming Medical University, Kunming, China.

Second Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, China.

出版信息

Front Oncol. 2018 Sep 26;8:413. doi: 10.3389/fonc.2018.00413. eCollection 2018.

Abstract

Growing evidence indicates that p53 can regulate the expression of miRNAs, particularly the miR-34 family members, which are described as potential tumor suppressors. Loss of miR-34 suppresses TP53-mediated cell death, whereas over expression of miR-34 induced apoptosis. The study designed to investigate the association between the pir-miR-34b/c rs4938723, TP53 Arg72Pro and the risk of glioma. We genotyped the two polymorphisms in175 glioma patients and 235 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing assay. Association analysis showed that the CC genotype of the pir-miR-34b/c rs4938723 was associated with a significantly decreased risk of glioma compared to the TT genotype (CC vs. TT: adjusted OR = 0.43;95% CI, 0.21-0.87, = 0.02). Moreover, a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 0.41; 95% CI, 0.21-0.81, = 0.007). In contrast, the CC genotype of the TP53 Arg72Pro was associated with a significantly increased risk of glioma compared to the GG genotype (CC vs. GG: adjusted OR = 1.73;95% CI, 1.04-2.89, = 0.04), and a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 2.00; 95% CI, 1.26-3.18, = 0.003). These findings suggest that the pri-miR-34b/c rs4938723CC and TP53 Arg72-Pro polymorphisms may be associated with the risk of glioma.

摘要

越来越多的证据表明,p53可以调节微小RNA(miRNA)的表达,尤其是miR-34家族成员,它们被认为是潜在的肿瘤抑制因子。miR-34缺失会抑制TP53介导的细胞死亡,而miR-34过表达则会诱导细胞凋亡。本研究旨在探讨pir-miR-34b/c rs4938723、TP53 Arg72Pro与胶质瘤风险之间的关联。我们采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和DNA测序分析法,对175例胶质瘤患者和235例健康对照者的这两种多态性进行了基因分型。关联分析显示,与TT基因型相比,pir-miR-34b/c rs4938723的CC基因型与胶质瘤风险显著降低相关(CC与TT:校正比值比=0.43;95%可信区间,0.21-0.87,P=0.02)。此外,在隐性模型中也观察到胶质瘤患者与对照者之间存在显著关联(比值比=0.41;95%可信区间,0.21-0.81,P=0.007)。相反,与GG基因型相比,TP53 Arg72Pro的CC基因型与胶质瘤风险显著增加相关(CC与GG:校正比值比=1.73;95%可信区间,1.04-2.89,P=0.04),并且在隐性模型中也观察到胶质瘤患者与对照者之间存在显著关联(比值比=2.00;95%可信区间,1.26-3.18,P=0.003)。这些发现表明,pri-miR-34b/c rs4938723CC和TP53 Arg72-Pro多态性可能与胶质瘤风险相关。

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