炎症相关miRNA 及其靶序列SNPs 与胃癌发生的分子流行病学研究

Helicobacter pylori-related inflammation is closely related to the occurrence and development of gastric cancer. Inflammation-associated microRNA（miRNA）and its target sequence single nucleotide polymorphisms plays an important role in inflammation-gene expression and regulation. Based on the preliminary studies and the established gastric cancer sample repository, this project aims to explore the inflammation-associated miRNA and its target sequence binding loci SNPs using bioinformatics; and to investigate the relationship between the miRNA and SNPs in its target sequence binding site and gastric cancer mechanism, by performing interaction analysis of single locus, the combined effect of multi-SNP and the miRNA-SNP through the method of case-control study and SNaPshot genotyping method; the adjustive function of inflammation-associated miRNA and its target sequence binding loci SNPs in the expression of inflammation factors to be researched through luciferase reporter system,real-time quantitative PCR and immuno- histochemistry technology. And eventually it can help to reveal the mechanism how miRNA participate the inflammation and the occurrence and development of gastric cancer and thus providing theoretical basis for the implementation of useful individualized prevention, intervention and therapies in the future.

幽门螺杆菌相关慢性炎症与胃癌的发生、发展关系密切，炎症相关miRNA 及其靶序列单核苷酸多态性是炎性基因表达调控的重要环节。本项目拟在前期研究工作及已建立胃癌相关样本资源库基础上，利用生物信息学发掘炎症相关miRNA 及其靶序列结合位点SNP；采用病例对照研究方法及SNaPshot基因分型技术，从单位点、多位点联合作用、miRNA-SNP位点相互作用，结合环境危险因素分析，探讨miRNA及其靶序列结合位点SNP与胃癌发生机制；并在此基础上通过荧光素酶报告系统、实时定量PCR、免疫组化等技术，探讨炎症相关miRNA 及其靶序列结合位点SNP在炎性因子表达的调控作用。揭示miRNA参与炎症及胃癌的发生、发展的机制，并为今后实施有效的个体化预防、干预和治疗提供理论依据。

幽门螺杆菌相关慢性炎症与胃癌的发生、发展关系密切，炎症相关miRNA 及其靶序列单核苷酸多态性是炎性基因表达调控的重要环节。研究通过探讨炎症相关miRNA及其靶序列结合位点SNP在炎性因子表达的调控作用，利用系统生物学思想，将基因表达谱、miRNA 表达谱这两类胃癌相关的高通量转录组学数据进行整合，应用生物信息学方法对其内部特征进行深入挖掘，鉴定若干靶向调控炎性基因的miRNA分子及其靶序列SNP标志物；课题基于慢性炎症与癌症相关的理论基础，结合两阶段病例－对照研究设计，以“胃癌与正常对照”和“正常对照－慢性萎缩性胃炎－肠上皮化生－异型增生到胃癌” 的发生过程，应用qRT-PCR、SNaPshot基因分型技术等，进行单个miRNA、单位点、多位点联合作用、miRNA-SNP位点相互作用、结合环境危险因素分析，探讨miRNA及其靶序列SNP与胃癌发生机制的相关性；并在此基础上通过荧光素酶报告系统、实时定量PCR、免疫组化等技术，探讨炎症相关miRNA及其靶序列结合位点的SNP在炎性因子表达的调控作用。揭示miRNA参与炎症与胃癌的发生、发展的机制，鉴定这些炎症与肿瘤间的桥梁分子、关键细胞成分，为炎症相关性肿瘤的早期诊断、预防和治疗提供分子靶标，为实施有效的个体化预防、干预和治疗等提供理论依据，也为构建胃癌风险预测模型、开展风险评估和人群预防提供了依据。