前期研究表明，核不均一核糖核蛋白A1（hnRNP A1，以下称A1）与慢性结肠炎及结肠癌患者的发病呈正相关，且敲低A1可下调炎-癌信号分子NF-κB, STAT3的活化，提示A1很可能促进慢性结肠炎的恶性转化。本项目拟进一步比较A1在慢性结肠炎和结肠癌不同组织中的表达差异，确认其与NF-κB, STAT3等分子的相关性；分别建立A1在巨噬细胞和结肠上皮细胞中的条件性敲除小鼠，诱发实验性结肠炎-癌模型，与野生型小鼠相比较，探讨炎、靶细胞中A1介导的信号转导网络及其与疾病进展指标的关联，从中提炼出A1作为炎-靶细胞实现相互作用的共性效应分子的特征，阐明其影响巨噬细胞活化、促进结肠上皮细胞过度增殖进而癌变的信号通路，确证A1具有调控NF-κB和STAT3这两条炎-癌相关通路的节点样功能；在此基础上考察靶向干预A1对实验性结肠炎-癌模型的抑制作用，为靶向治疗炎症相关肿瘤提供理论依据。

Previous studies show that hnRNP A1 is positively related to the incidence of Crohn''s disease and colon cancer, and the knock-down of hnRNP A1 results in inactivation of NF-κB and STAT3, suggesting the malignant transformation of chronic colitis can be exacerbated by hnRNP A1. In the present study, the expression of hnRNP A1 was further compared in different tissues from chronic colitis and colon cancer and the relationships between hnRNP A1 and the key inflammation-cancer molecules such as NF-κB and STAT3 were examined. Then, the conditional knockout mice of hnRNP A1 in inflammatory cells (macrophages) and target cells (colonic epithelial cells) were established and the roles of hnRNP A1 on the experimental colitis-related colon cancer model as well as the interaction between macrophages and colonic epithelial cells were explored. Furthermore, the molecular mechanisms of the activation of macrophage, the excessive proliferation, anti-apoptosis and carcinogenesis of colonic epithelial cells as well as the regulation of NF-κB and STAT3 pathways by hnRNP A1 were investigated. Finally, the effect of targeted intervention of hnRNP A1 in the experimental colitis-related colon cancer model was also examined. This study provides a theoretical basis for targeted therapy of inflammation-associated tumors.