RegIII信号通路与SOCS3甲基化协同调控胰腺炎症恶性转化的分子机制研究

项目名称： RegIII信号通路与SOCS3甲基化协同调控胰腺炎症恶性转化的分子机制研究

项目编号： No.91229114

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 向明

作者单位： 华中科技大学

项目金额： 85万元

中文摘要： 炎症微环境下表达上调的再生基因RegIII可对炎症发挥有效的保护作用；然而在非可控性炎症中Reg III的高表达和分泌又与人恶性胰腺癌的发生密切相关。因此RegIII具有抗炎和促恶性转化的双重作用。RegIII的基因结构和功能使其参与炎症恶性转化的核心调控系统IL-6/ JAK/STAT3信号通路。胰腺癌组织中SOCS3甲基化又常与RegIIImRNA表达协同出现。为阐明RegIII相关的促慢性炎症恶性转化的复杂调控网络以及SOCS3基因所起的关键作用，本课题拟通过差示分析临床胰腺癌旁正常/癌旁炎症/癌组织中RegIII-SOCS3共表达分子；结合体外和体内方法，研究胰腺恶性转化过程中RegIII基因表达及其关联信号通路关键分子的动态变化和作用，以及SOCS3甲基化对RegIII信号通路激活后效应的影响，揭示RegIII调控通路和SOCS3甲基化协同促发胰腺非可控炎症恶性转化的新分子机制。

中文关键词： REG3；SOCS3；慢性胰腺炎恶性转化；信号通路；免疫调控

英文摘要： Regenerating gene（Reg）III is upregulated in the inflammatory microenvironment and provides effective protection against inflammation. However, Reg III also plays a key role in the development of malignant human pancreatic cancer. Thus, Reg III has the dual function of anti-inflammation and promoting malignant transformation. The structure and function of Reg III gene allow Reg III to be involved in the core control system of inflammation-linked carcinogenesis -- IL-6/ JAK/STAT3 signaling pathway. SOCS3 methylation and the expression of RegIII mRNA always occurred together in pancreatic cancer tissues. To clarify the RegIII-related complicated regulatory network and the key role of SOCS3 gene in inflammation-linked carcinogenesis, this research will use analysis of differential expressed genes in pancreatic cancer tissues / and their adjacent normal/ inflammatory tissues to identify RegIII-related molecules; study RegIII gene expression, the dynamical change and effect of key molecules in RegIII-related signaling pathway, and the influence of SOCS3 methylation on the final effect of activated RegIII signals. This research is to reveal the new molecular mechanism of the synergism of RegIII signaling pathways and SOCS3 methylation in the regulation of inflammation-linked pancreatic carcinogenesis.

英文关键词： REG3；SOCS3；tumorigenesis from chronic pancreatitis；signal pathway；immunoregulation