microRNA 结合位点单核苷酸多态性与鼻咽癌风险的相关性研究。
Risk of Nasopharyngeal Carcinoma Associated with Single Nucleotide Polymorphisms in the MicroRNA Binding Site of .
机构信息
Department of Otolaryngology, Wenzhou People's Hospital, Wenzhou, China.
Department of Otolaryngology, Huzhou Central Hospital, Huzhou, China.
出版信息
Genet Test Mol Biomarkers. 2020 Aug;24(8):508-519. doi: 10.1089/gtmb.2019.0278. Epub 2020 Jul 9.
Serum/glucocorticoid regulated kinase is a serine/threonine kinase that is involved in regulating cell proliferation, apoptosis, the cell cycle, and ion channel function. The aim of this study was to analyze the relationship between single nucleotide polymorphisms (SNPs) in the microRNA (miRNA) binding site of the gene and the risk of nasopharyngeal carcinoma (NPC). Three loci, rs77572541, rs11994200, and rs78158330, were genotyped in 226 NPC patients and 226 healthy controls via Sanger sequencing. Quantitative real-time polymerase chain reaction was used to analyze levels of messenger RNA (mRNA), hsa-miR-3529-5p, hsa-miR-379-5p, hsa-miR-498, hsa-miR-4320, and hsa-miR-590-3p. Western blot analysis was used to assess serum and glucocorticoid regulated kinase 3 (SGK3) protein expression. rs77572541 locus G allele carriers were 3.47 times more likely to develop NPC than carriers of the A allele (95% confidence interval [CI] = 1.98-6.09, < 0.01). The rs11994200 locus C allele was a major risk factor for NPC (odds ratio = 2.68, 95% CI = 1.63-4.39, < 0.01). Similarly, carriers of the C allele of the rs78158330 locus were 3.36 times more likely to develop NPC than those with the T allele (95% CI = 1.96-5.73, < 0.01). The SGK3 protein was highly expressed in NPC. The rs77572541 locus G allele is the target of hsa-miR-379-5p and hsa-miR-3529-5p, but the A allele is not. The rs11994200 locus C allele was the target of hsa-miR-4320, and the G allele was the target of hsa-miR-498. The rs78158330 locus T allele was the target of hsa-miR-590-3p. Hsa-miR-3529-5p, hsa-miR-379-5p, and hsa-miR-4320 were down-regulated in NPC tissues ( < 0.01), whereas hsa-miR-498 and hsa-miR-590-3p were highly expressed ( < 0.01). SNPs at the loci rs77572541, rs11994200, and rs78158330 are significantly associated with the risk for NPC. These effects may be related to the influence of miRNAs on different alleles, but this needs to be verified both and .
血清/糖皮质激素调节激酶是一种丝氨酸/苏氨酸激酶，参与调节细胞增殖、凋亡、细胞周期和离子通道功能。本研究旨在分析基因 miRNA 结合位点的单核苷酸多态性 (SNP) 与鼻咽癌 (NPC) 风险之间的关系。通过 Sanger 测序，在 226 名 NPC 患者和 226 名健康对照中，对三个位点 rs77572541、rs11994200 和 rs78158330 进行了基因分型。采用实时定量聚合酶链反应分析 信使 RNA (mRNA)、hsa-miR-3529-5p、hsa-miR-379-5p、hsa-miR-498、hsa-miR-4320 和 hsa-miR-590-3p 的水平。采用 Western blot 分析检测血清和糖皮质激素调节激酶 3 (SGK3) 蛋白表达。rs77572541 位点 G 等位基因携带者发生 NPC 的风险是 A 等位基因携带者的 3.47 倍 (95%置信区间 [CI] = 1.98-6.09， <0.01)。rs11994200 位点 C 等位基因是 NPC 的主要危险因素 (比值比 = 2.68，95%CI = 1.63-4.39， <0.01)。同样，rs78158330 位点 C 等位基因携带者发生 NPC 的风险是 T 等位基因携带者的 3.36 倍 (95%CI = 1.96-5.73， <0.01)。SGK3 蛋白在 NPC 中高表达。rs77572541 位点 G 等位基因是 hsa-miR-379-5p 和 hsa-miR-3529-5p 的靶基因，但 A 等位基因不是。rs11994200 位点 C 等位基因是 hsa-miR-4320 的靶基因，G 等位基因是 hsa-miR-498 的靶基因。rs78158330 位点 T 等位基因是 hsa-miR-590-3p 的靶基因。hsa-miR-3529-5p、hsa-miR-379-5p 和 hsa-miR-4320 在 NPC 组织中表达下调 ( <0.01)，而 hsa-miR-498 和 hsa-miR-590-3p 表达上调 ( <0.01)。rs77572541、rs11994200 和 rs78158330 位点的 SNP 与 NPC 风险显著相关。这些影响可能与 miRNA 对不同等位基因的影响有关，但这需要进一步验证。
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