Genetic predisposition to papillary thyroid carcinoma is mediated by a long non-coding RNA TINCR enhancer polymorphism
Genetic predisposition to papillary thyroid carcinoma is mediated by a long non-coding RNA TINCR enhancer polymorphism
复制标题
甲状腺乳头状癌的遗传易感性是由长链非编码 RNA TINCR 增强子多态性介导的
DOI：
10.1016/j.intimp.2022.108796
复制
发表时间：
2022-04-27
影响因子：
5.6
通讯作者：
Zhang，Lin
中科院分区：
文献类型：
--
作者：
Wang，Qiang;Huang，Hong;Zhang，Lin
增强子区域的单核苷酸多态性（SNP）已被证明赋予改变的增强子活性、异常基因表达和癌症易感性。在这项研究中，我们的目的是检查SNP，rs 8101923，在终末分化诱导的非编码RNA（TINCR）和甲状腺乳头状癌（PTC）的风险之间的关联。收集了559例PTC患者和445例健康人的血液样本。采用聚合酶链反应-限制性片段长度多态性分析对rs 8101923进行基因分型。通过实时荧光定量PCR和双荧光素酶报告基因分析评价rs 8101923对TINCR表达和增强子活性的影响。染色质免疫沉淀法测定AP-2α与TINCR增强子的结合。rs 8101923 G等位基因与PTC的高风险显著相关（校正OR = 1.37; 95%CI：1.15-1.64）。rs 8101923与转录水平和增强子活性增加有关（P< 0.05）。转录因子AP-2α与TINCR的rs 8101923位点的增强子区结合，促进PTC细胞增殖。这些结果提示rs 8101923是PTC发病的一个危险因素，为解释rs 8101923危险等位基因易感PTC的机制提供了证据。
Single nucleotide polymorphisms (SNPs) in the enhancer region have been demonstrated to confer to altered enhancer activities, aberrant gene expression, and cancer susceptibility. In this study, we aimed to examine the association between an SNP, rs8101923, within terminal differentiation-induced non-coding RNA (TINCR) and the risk of papillary thyroid carcinoma (PTC). Blood samples from 559 patients with PTC and 445 healthy individuals were collected. The rs8101923 was genotyped by using polymerase chain reaction-restriction fragment length polymorphism assay. The impact of the rs8101923 onTINCRexpression and enhancer activity was evaluated by quantitative real-time PCR and dual-luciferase reporter assay. The binding of AP-2α toTINCRenhancer was determined by chromatin immunoprecipitation. The rs8101923 G allele was significantly associated with a higher risk of PTC (adjusted OR = 1.37; 95% CI: 1.15–1.64). Mechanistically, the rs8101923 was related to increased transcriptional levels and enhancer activities (P< 0.05). Transcription factor AP-2α binds to the enhancer region ofTINCRcontaining the rs8101923 locus, and promotes cell proliferation in PTC. These findings suggest the rs8101923 as a risk factor in the pathogenesis of PTC, which provides evidence for explaining the mechanism of the rs8101923 risk allele predisposing to PTC.