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）是结直肠癌（CRC）发展的众所周知的危险因素。关于UC全基因组关联研究（GWAS）和候选基因研究，已经确定了各种易感基因座。特别地，确定了对六个UC GWAS数据集进行的荟萃分析，包括干扰素调节因子-5（IRF-5）。 IRF-5充当1型干扰素的转录激活剂，因此能够调节多种基因，这些基因编码对细胞因子诱导的细胞可塑性，细胞增殖和分化的影响不同的蛋白质。现在，我们可以证明IRF-5在UC，结肠炎相关的结直肠癌（CAC）和零星CRC中的表达。 IRF-5的表达不仅限于特定的细胞类型，并且在间接不同，因为结直肠癌细胞，T细胞，B细胞，巨噬细胞以及肿瘤细胞可能表达IRF-5。几个指标，包括我们自己在小鼠和人类疾病中的初步工作，表明IRF-5在结直肠癌的发展中具有病理意义。该项目的目的是证明IRF-5在肠道肿瘤发生中的细胞类型特异性作用。