GJB2/hnRNPA2通过调控β-catenin mRNA稳定性促进胰腺癌转移的机制研究

缺氧是促进肿瘤转移的重要因素之一，也是胰腺癌组织的重要特征，但是缺氧如何促进胰腺癌的转移，目前还不太清楚。我们通过TCGA胰腺癌数据库挖掘和分析，发现缺氧可以促进胰腺癌缝隙连接蛋白β2（GJB2）上调，进一步验证发现GJB2能够促进胰腺癌细胞的迁移和侵袭能力，调控β-catenin mRNA稳定性，促进胰腺癌细胞EMT表型，而且可能与hnRNPA2发生相互作用。因此，我们提出研究假说：缺氧诱导上调的GJB2能结合并保护hnRNPA2，减少β-catenin mRNA的降解，使β-catenin转位入核增多，促进胰腺癌细胞的EMT，导致胰腺癌细胞的侵袭转移能力增强。本研究从β-catenin基因转录后调控角度，探讨GJB2促进胰腺癌侵袭转移的机制，解释为什么缺氧能促进胰腺癌转移，为胰腺癌的诊断和治疗提供一个新的研究视角。

Hypoxia is one of the important factors to promote tumor metastasis and an important feature of pancreatic cancer tissues. However, it is not clear how hypoxia can promote pancreatic cancer metastasis. Through mining and analysis of the TCGA pancreatic cancer database, we found that hypoxia can promote the expression of gap junction protein β2 (GJB2) in pancreatic cancer. It was also verified that GJB2 can promotes the invasion ability of pancreatic cancer cells, regulates the stability of β-catenin mRNA, and promotes the EMT phenotype of cancer cells by interacting with hnRNPA2. Based on this, a scientific hypothesis is proposed: hypoxia-induced up-regulated GJB2 can bind and protect hnRNPA2, reduce β-catenin mRNA degradation, activate β-catenin signaling pathway by translocating into the nuclear, thereby promoting pancreatic cancer cell EMT and invasion. From the perspective of gene post-transcriptional regulation, this research project explore the mechanism of GJB2 promoting pancreatic cancer invasion and metastasis, and explain why hypoxia promotes pancreatic cancer metastasis, providing a new perspective for the diagnosis and treatment of pancreatic cancer.