胰腺癌是严重危害人类健康的恶性肿瘤。HIF-1α表达水平与胰腺导管腺癌的病理分级、淋巴结转移和不良预后呈正相关，但其在胰腺癌中独特的组成型高表达的机制尚不明确。课题组前期研究发现多个 HIF-1α相关SNP参与胰腺癌HIF-1α表达调控，部分SNP被证明作为胰腺癌易感基因型。近年研究发现micro-RNA是参与细胞内转录后调控的重要分子，靶序列的单核苷酸多态性变异会破坏micro-RNA的结合与转录后调控，影响靶基因的表达。本项目选取胰腺癌乏氧微环境核心调控因子 HIF-1α 3'非编码区micro-RNA靶序列相关SNP，探讨不同等位基因型对胰腺癌细胞HIF-1αmRNA及蛋白表达水平的影响，进一步探索micro-RNA相关SNP对胰腺癌细胞恶性生物学行为的影响，并通过分子生物学和细胞学功能实验分析其作用模式和调控机制，这些研究将为探索胰腺癌分子标志物和寻找治疗靶标提供有益帮助。

Pancreatic cancer is a highly aggressive disease with a grim prognosis. HIF-1α expression correlates with clinicopathological parameters of pancreatic cancer, such as tumor's grades, stages and lymph-node metastasis. HIF-1α protein was constitutively expressed in pancreatic cancer tissues and cell lines. The molecular events underlying this remain poorly defined. We have found that Polymorphisms in the hypoxia-inducible factor-1α gene confer susceptibility to pancreatic cancer. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that regulate gene expression. MiRNAs play key roles in regulating the translation and degradation of mRNAs through base pairing to partially complementary sites in the 3'UTR of the message. Polymorphisms in 3'UTR of several genes have been reported to affect gene expression, but the mechanism is not fully understood. In this study, we investigated the effect of SNPs, which locate in the 3'UTR of HIF-1α. We want to use the molecular biology experiments to test the regulation mechanisms of the SNP, and evaluation the SNP genotypes, which was a risk genotype for pancreatic cancer development and was also associated with pancreatic cancer clinicopathological parameters and poor survival. This study may provide a new tumor marker or potential target for pancreatic cancer treatment.