Yu Yulong, Yin Han, Wu Bili, Zhao Weiheng, Wang Yuan, Aili Aifeina, Yang Mu, Yu Qianqian, Yuan Xianglin
Department of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Biomed Sci. 2025 Jan 6;32(1):5. doi: 10.1186/s12929-024-01097-4.
The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum (F. nucleatum, FN) being found in high abundance in colorectal cancer tissues. Previous research has emphasized the significant role of F. nucleatum in the occurrence of CRC. However, the impact of F. nucleatum on CRC liver metastasis has not been well understood.
The effects of F. nucleatum on metastasis ability of CRC cell were evaluated in vitro were examined by wound-healing assay and transwell assay. The mouse model of CRC liver metastasis was constructed by spleen injection, and the degree of liver metastasis was assessed by in vivo bioluminescence imaging. The gene expression changes in CRC cells after co-culture with F. nucleatum was analyzed through transcriptome sequencing. qRT-PCR and Western Blot assays were performed to validate the expression of related genes and proteins.
The metastasis ability of CRC cells was significantly enhanced after co-culture with F. nucleatum in vitro. In the mouse model, F. nucleatum also promoted the development of liver metastasis in CRC. Mechanistically, F. nucleatum infection increased the expression of IL-8 by downregulated the level of miR-5692a, a regulatory microRNA of IL-8. This led to the activation of the ERK pathway and resulted in the epithelial-mesenchymal transition (EMT) of CRC cells.
Our results suggest that F. nucleatum promotes CRC liver metastasis by inducing epithelial-mesenchymal transition through the miR-5692a/IL-8 axis. These findings provide new insights for the prevention and treatment of colorectal cancer liver metastasis.
肠道微生物群与结直肠癌（CRC）之间的关联已得到广泛研究，在结直肠癌组织中发现具核梭杆菌（F. nucleatum，FN）含量很高。先前的研究强调了具核梭杆菌在结直肠癌发生中的重要作用。然而，具核梭杆菌对结直肠癌肝转移的影响尚未得到充分了解。
通过伤口愈合试验和Transwell试验在体外评估具核梭杆菌对CRC细胞转移能力的影响。通过脾脏注射构建CRC肝转移小鼠模型，并通过体内生物发光成像评估肝转移程度。通过转录组测序分析具核梭杆菌与CRC细胞共培养后CRC细胞中的基因表达变化。进行qRT-PCR和蛋白质免疫印迹试验以验证相关基因和蛋白质的表达。
在体外与具核梭杆菌共培养后，CRC细胞的转移能力显著增强。在小鼠模型中，具核梭杆菌也促进了CRC肝转移的发展。机制上，具核梭杆菌感染通过下调IL-8的调节性微小RNA miR-5692a的水平增加了IL-8的表达。这导致ERK途径的激活，并导致CRC细胞的上皮-间质转化（EMT）。
我们的结果表明，具核梭杆菌通过miR-5692a/IL-8轴诱导上皮-间质转化来促进CRC肝转移。这些发现为结直肠癌肝转移的预防和治疗提供了新的见解。
