核梭杆菌通过miR-5692a/IL-8轴诱导上皮-间质转化促进结直肠癌肝转移。

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2025-01-06 DOI:10.1186/s12929-024-01097-4
Yulong Yu, Han Yin, Bili Wu, Weiheng Zhao, Yuan Wang, Aifeina Aili, Mu Yang, Qianqian Yu, Xianglin Yuan
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引用次数: 0

摘要

背景:肠道微生物群与结直肠癌(CRC)之间的关系已被广泛研究,在结直肠癌组织中发现了高丰度的核梭杆菌(F. nucleatum, FN)。以往的研究强调了具核梭菌在结直肠癌发生中的重要作用。然而,核梭菌对结直肠癌肝转移的影响尚不清楚。方法:采用体外创面愈合法和transwell法观察核梭菌对结直肠癌细胞转移能力的影响。采用脾注射法建立小鼠结直肠癌肝转移模型,采用体内生物发光显像法评估小鼠肝转移程度。通过转录组测序分析结直肠癌细胞与具核梭菌共培养后基因表达的变化。采用qRT-PCR和Western Blot检测相关基因和蛋白的表达。结果:结直肠癌细胞与具核梭菌体外共培养后转移能力明显增强。在小鼠模型中,核梭菌也促进了结直肠癌肝转移的发生。在机制上,核梭菌感染通过下调IL-8的调控microRNA miR-5692a的水平来增加IL-8的表达。这导致ERK通路的激活,并导致CRC细胞的上皮-间质转化(EMT)。结论:我们的研究结果表明,核梭菌通过miR-5692a/IL-8轴诱导上皮-间质转化,从而促进结直肠癌肝转移。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。
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Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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