Abstract: Objective To explore the effects and potential mechanism of Fusobacterium nucleatum （Fn） on colorectal cancer cells. Methods The subjects were from the patients who underwent colonoscopy in the outpatient department of Shenzhen People's Hospital. A total of 15 patients with colorectal cancer （grouped according to preoperative and postoperative） and 15 people with colonoscopy without colorectal diseasewere selected. qPCR was performed to detect the abundance of Fn in fecal samples. The proliferation, migration and invasion of colorectal cancer cells （HCT116, SW480） were detected by CCK-8 and transwell assay. The expression of related genes to colorectal cancercells was analyzed by whole transcriptome microarray after infecting with Fn. Screening and functional verification of significant differential genes. Results the composition of intestinal flora in operated group was close to that in healthy group. The Fn abundancein CRC group was significantly higherthan that in both operated group and healthy group. Fn can promote the proliferation, migration and invasion of colorectal cancer cells. Microarray analysis showed that LCN2 was the most differentially expressed gene after Fn infection in colorectal cancer cells. Overexpression of LCN2 inhibited the proliferation activity and migration and invasion ability of colorectal cancer cells, Fn reduced the inhibitory effect of LCN2 on colorectal cancer cells. Conclusion Fn can promote the proliferation and migration of colorectal cancer cells by down-regulating the expression of LCN2, which provide some supports for LCN2 to be a prevention and treatment target for Fn-related colorectal cancer

Key words: Fusobacterium nucleatum （Fn）, proliferation, invasion, migration, LCN2, colorectal cancer

摘要： 目的 探究具核梭杆菌（Fn）对结直肠癌细胞的影响机制。方法 研究对象来自深圳市人民医院门诊的肠镜受检者,共选取15例结直肠癌患者（按术前与术后分组）,和15例无结直肠疾病的肠镜受检者（健康组）,qPCR检测粪便样品中具核梭杆菌的丰度;CCK-8和Transwell分别检测具核梭杆菌对结直肠癌细胞（HCT116、SW480）增殖和迁移侵袭的影响;转录组微阵列分析具核梭杆菌对结直肠癌细胞相关基因表达的影响;筛选差异基因,并加以功能验证。结果 qPCR结果显示具核梭杆菌在术前组中的丰度显著高于术后组和健康组;具核梭杆菌能够促进结直肠癌细胞增殖、迁移和侵袭;微阵列分析结果显示脂质运载蛋白-2（LCN2）mRNA相对含量在具核梭杆菌感染的结直肠癌细胞中显著下调。过表达LCN2能够抑制结直肠癌细胞增殖活性和迁移侵袭能力,而具核梭杆菌能够可以抑制LCN2的mRNA和蛋白表达,减弱LCN2对结直肠癌细胞的抑制效应。结论 具核梭杆菌能够通过下调LCN2的表达来促进结直肠癌细胞增殖和迁移侵袭能力,为LCN2作为预防和治疗与具核梭杆菌相关的结直肠癌的靶点提供了相关理论依据。

关键词: 具核梭杆菌, 结直肠癌, LCN2, 迁移, 增殖, 侵袭