Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China; Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Department of Pharmacology, Dazhou Vocational and Technical College, Dazhou, Sichuan 635001, PR China.
Int Immunopharmacol. 2022 Aug;109:108796. doi: 10.1016/j.intimp.2022.108796. Epub 2022 Apr 27.
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 on TINCR expression and enhancer activity was evaluated by quantitative real-time PCR and dual-luciferase reporter assay. The binding of AP-2α to TINCR enhancer 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 of TINCR containing 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.
单核苷酸多态性（SNPs）在增强子区域的作用已被证明可以改变增强子活性、异常基因表达和癌症易感性。在这项研究中，我们旨在研究位于终端分化诱导非编码 RNA（TINCR）内的 SNP（rs8101923）与甲状腺乳头状癌（PTC）风险之间的关联。采集了 559 例 PTC 患者和 445 例健康个体的血液样本。采用聚合酶链反应-限制性片段长度多态性分析检测 rs8101923 基因型。通过定量实时 PCR 和双荧光素酶报告基因检测评估 rs8101923 对 TINCR 表达和增强子活性的影响。通过染色质免疫沉淀测定 AP-2α 与 TINCR 增强子的结合。rs8101923 的 G 等位基因与 PTC 的风险显著相关（调整后的 OR = 1.37；95%CI：1.15-1.64）。从机制上讲，rs8101923 与转录水平和增强子活性的增加有关（P < 0.05）。转录因子 AP-2α 结合到包含 rs8101923 位点的 TINCR 增强子区域，并促进 PTC 中的细胞增殖。这些发现表明 rs8101923 是 PTC 发病机制的风险因素，为解释 rs8101923 风险等位基因易患 PTC 的机制提供了证据。
