The cell-specific role of Interferon regulatory factor-5 for tumor cell plasticity and tumor progression during ulcerative colitis-associated and spontaneous colon tumorigenesis

干扰素调节因子 5 在溃疡性结肠炎相关和自发性结肠肿瘤发生过程中对肿瘤细胞可塑性和肿瘤进展的细胞特异性作用

• 批准号: 319450600
• 负责人: Professor Dr. Stefan Fichtner-Feigl
• 金额: --
• 依托单位: Klinik für Allgemein- und Viszeralchirurgie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/319450600?language=en
• 关键词: cell; specific; role; Interferon; regulatory

Ulcerative colitis (UC) is a well-known risk factor for the development of colorectal cancer (CRC). With regards to UC genome-wide association studies (GWAS) and candidate gene studies have identified a variety of susceptibility loci. In particular, a conducted meta-analysis of six UC GWAS datasets additional risk loci, including Interferon regulatory factor-5 (IRF-5), were identified. IRF-5 functions as transcriptional activators for type-1 interferons and, thus, is capable of modulating multiple genes that encode proteins with diverse effects on cytokine-induced cell plasticity, cell proliferation and differentiation. We can now demonstrate the expression of IRF-5 in UC, colitis-associated colorectal cancer (CAC) and in sporadic CRC. The expression of IRF-5 is not limited to a particular cell type and varies interindividually, as colorectal cancer cells, T cells, B cells, macrophages, as well as tumor cells potentially express IRF-5. Several indicators, including our own preliminary work in mice and human disease, suggest a pathological significance of IRF-5 in the development of colorectal carcinomas. The aim of this project is to demonstrate cell type-specific roles of IRF-5 in intestinal tumorigenesis.

溃疡性结肠炎(UC)是公认的结直肠癌(CRC)的危险因素。关于UC，全基因组关联研究和候选基因研究已经确定了各种易感基因。特别是，对六个UC Gwas数据集进行的荟萃分析确定了额外的风险基因，包括干扰素调节因子-5(IRF-5)。IRF-5作为1型干扰素的转录激活剂，能够调节多种编码蛋白质的基因，对细胞因子诱导的细胞可塑性、细胞增殖和分化有不同的影响。我们现在可以证明IRF-5在UC、结肠炎相关性结直肠癌(CAC)和散发性结直肠癌中的表达。由于结直肠癌细胞、T细胞、B细胞、巨噬细胞以及肿瘤细胞都可能表达IRF-5，因此IRF-5的表达不限于特定的细胞类型，而且各细胞之间存在差异。一些指标，包括我们自己在小鼠和人类疾病中的初步工作，表明了IRF-5在结直肠癌发生发展中的病理学意义。这个项目的目的是证明IRF-5在肠道肿瘤发生中的细胞类型特异性作用。