Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma
Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma
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Casp3 microRNA 靶位点 (1049216) SNP 与宫颈鳞状细胞癌风险和进展的关联
DOI：
10.1097/igc.0000000000000881
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发表时间：
2017-02-01
影响因子：
4.8
通讯作者：
Guo, Wei
中科院分区：
文献类型：
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作者：
Guo, Xin;Dong, Zhiming;Guo, Wei
目的：本研究探讨miRNA靶点caspase-3 rs1049216 （C > T）的单核苷酸多态性（SNP）与宫颈癌发生、发展的关系。材料与方法：采用聚合酶链反应-限制性片段长度多态性方法，对515例宫颈鳞状细胞癌患者和415例对照组的caspase-3 rs1049216基因型和分布进行了分析。在其他实验中，我们将携带Tor C等位基因和/或miRNA模拟物的荧光素酶报告质粒转染到人宫颈细胞系（HeLa和C- 33a）中，分析其在调节caspase3表达中的作用。采用免疫组化方法检测515例宫颈鳞癌患者肿瘤组织中caspase-3蛋白表达水平。结果：我们发现，TT基因型caspase-3 rs1049216可显著降低宫颈癌的风险（校正优势比为0.35；95%可信区间为0.154Y0.581），并可能与宫颈癌的进展有关。外周血单核细胞和肿瘤组织中，TT基因型的caspase-3表达高于CC/CT基因型。另外的荧光素酶分析表明，与转染细胞中的C等位基因相比，rs1049216变异T等位基因与更高的荧光素酶活性相关，并且当与mirna共转染时，miRNA-181a可以下调含有C等位基因的细胞中的荧光素酶活性，而与T等位基因相比，这种情况在选择的其他mirna存在时没有发生。结论：这些数据表明，通过上调caspase-3的表达，caspase-3 rs1049216 TT基因型不仅与宫颈癌的发生风险有关，而且与宫颈癌的进展有关。
Objective: In the present study, we investigated the relationship between the single-nucleotide polymorphism (SNP) of caspase-3 rs1049216 (C > T), a miRNA target site, and the risk and progression of cervical cancer.Materials and Methods: Using polymerase chain reactionYrestriction fragment length polymorphism, we evaluated the genotype and distribution of caspase-3 rs1049216 in 515 patients with cervical squamous cell cancer and 415 controls. In additional experiments, we transfected luciferase reporter plasmids carrying Tor C allele and/or miRNA mimics into the human cervical cell lines (HeLa and C-33A) to analyze its roles in the regulation of caspase3 expression. By immunohistochemistry, the protein level of caspase-3 expression was examined in tumor tissues from 515 patients with cervical squamous cell cancer.Results: We found that the TT genotype of caspase-3 rs1049216 conferred a significantly decreased risk of cervical cancer (adjusted odds ratio, 0.35; 95% confidence interval, 0.154Y0.581) and may be associated with the progression of this cancer. Although the expression of caspase-3 in the TT genotypewas higher than that in CC/CT genotype in peripheral blood mononuclear cells and tumor tissues. Additional luciferase analysis showed that the rs1049216 variant T allelewas associatedwith significantly higher luciferase activity, comparedwith the C allele in the transfected cells, andwhen cotransfected with miRNAs, miRNA-181a could downregulate the luciferase activity in the cells that transfected the construct containing C allele, compared with T allele, which had not happened in the presence of other miRNAs selected.Conclusions: These data indicate that through upregulating the expression of caspase-3, the TT genotype of caspase-3 rs1049216 can be associated with not only the risk of cervical cancer but also the progression of this cancer.