HIF-1α–URG11信号通路促进上皮–间质转化在胰腺癌侵袭转移中的价值研究

It is significantly important to explore the molecular mechanism of invasion and metastasis of pancreatic cancer for its survival rate improvement. URG11 (Up Regulation Gene 11), a novel gene, was first reported to be highly expressed in pancreatic cancer by our group, which was a unfavorable biomarker for its prognosis. Our previous studies have found that URG11 was correlated with tumor size, lymph nodes metastasis, blood vessel invasion and early recurrence. Pathological detections revealed it could regulate the expression of epithelial-mesenchymal transformation (EMT) markers in a large cohort of specimens. URG11 can promote the invasion and metastasis of pancreatic cancer cells. However, the role of URG11 in pancreatic cancer remains largely elusive. Recently, we demonstrated that hypoxia increased the expression of URG11, which could lead to EMT. Bioinformatics analysis showed there were three hypoxia-inducible factor-1 alpha (HIF-1 α) components in URG11 promoter region. Based on the above results, we infer that URG11 is a target gene of HIF-1 α, and is responsible for HIF-1 α-induced invasion and metastasis by promoting EMT. This research shed light on the biologic functions of URG11, and is significant in understanding the molecular mechanisms of invasion and metastasis of pancreatic cancer.

探究胰腺癌侵袭转移分子机制对提高患者生存率意义重大。URG11（Up Regulation Gene 11）是申请者首先在国际上报道的在胰腺癌中高表达，并与患者预后负相关的新基因。前期工作中我们发现URG11与肿瘤的体积、淋巴结转移、血管侵袭和早期复发等表现相关，大样本病理检测揭示其与上皮-间质转化（EMT）标志物表达有关；细胞水平研究显示URG11可促进胰腺癌侵袭转移；但URG11促进胰腺癌侵袭转移的分子机制尚未完全阐明。结合我们近期的发现：缺氧可使URG11的表达显著升高；URG11可促进EMT；生物信息学发现URG11启动子区域有3个缺氧诱导因子1α（HIF-1α）的结合元件。基于以上工作基础，我们推测：URG11是HIF-1α的一个靶基因，URG11通过促进EMT来介导HIF-1α引起的胰腺癌侵袭转移。本研究对于阐明URG11基因的功能及其在胰腺癌侵袭转移中的分子机制具有重要意义。

URG11（Up Regulation Gene 11）是申请者报道的在胰腺癌中高表达，并与患者预后负相关的新基因。我们发现URG11与肿瘤的体积、淋巴结转移、血管侵袭和早期复发等表现相关，病理检测揭示了其与上皮-间质转化（EMT）标志物表达有关；细胞水平研究显示了URG11可促进胰腺癌侵袭转移。我们的研究发现：缺氧可使URG11的表达显著升高；URG11可促进EMT；生物信息学发现了URG11启动子区域有3个缺氧诱导因子1α（HIF-1α）的结合元件。URG11是HIF-1α的一个靶基因，URG11通过促进EMT介导了HIF-1α引起的胰腺癌侵袭转移。