炎症和肿瘤发生的分子调控机制是结肠癌尤其是炎性肠病相关结肠癌中的重大科学问题，肠道巨噬细胞的活化在炎性肠病中发挥关键作用，其活化的调控机制目前受广泛关注。DDX家族分子在天然免疫和炎症中发挥重要调控作用，如DDX58缺陷小鼠能够自发肠道炎症。然而，目前仍缺乏DDX家族分子在炎症调控中的系统研究，在结肠癌炎症和肿瘤发生中仍无报道。据此，我们在AOM/DSS小鼠结肠癌炎症和肿瘤发生模型中，系统检测了DDX家族分子的表达，发现DDX39在癌组织肠道巨噬细胞中表达显著降低。我们进而构建了DDX39条件敲除小鼠，发现DDX39全身敲除和巨噬细胞敲除的小鼠结肠癌诱导发生显著增加，而肠上皮敲除小鼠无显著变化，提示DDX39极有可能通过调控肠道巨噬细胞介导的炎症反应，进而调控结肠癌发生。据此，本研究拟探求DDX39在巨噬细胞活化及其介导的炎症和肿瘤发生中的调控机制，从炎性肠病调控角度提出结肠癌发生新机制。

Molecular regulatory mechanisms of inflammation and carcinogenesis are important scientific research field in inflammatory bowel disease (IBD)-related colorectal cancer. Bowel macrophages play important roles in IBD, and the regulatory mechanisms of its activation have attracted much attention. DDX family members are important regulators in innate immune response and inflammation. For example, RIG-I (DDX58)-deficient mice can develop spontaneous colitis. However, the roles of DDX family members in the regulation of inflammation still need systemic investigation, especially for IBD-related colorectal cancer carcinogenesis. Hence, we examined the expression of DDX family members in bowel macrophages of AOM/DSS-induced colon cancer, and found that DDX39 expression in bowel macrophages was significantly inhibited. Based on this data, we constructed the conditional knockout mouse of DDX39, and generated macrophage-specific and intestinal epithelium-specific knockout mouse of DDX39. We found that AOM/DSS-induced colon cancer was significantly increased by macrophage-specific DDX39 deficiency, but not intestinal epithelium-specific DDX39 deficiency. Hence, DDX39 expression in macrophages may be important for the IBD-related colon cancer carcinogenesis. Based on these findings, we intend to investigate the roles of DDX39 in the regulation of macrophage activation, inflammation, and IBD-related colon cancer carcinogenesis, so as to suggest new regulatory mechanisms of inflammation and cancer in the colon.