Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7

• Published in: Gut microbes Vol. 11; no. 3; pp. 511 - 525
• Main Authors: Chen, Shujie, Su, Tingting, Zhang, Ying, Lee, Allen, He, Jiamin, Ge, Qiwei, Wang, Lan, Si, Jianmin, Zhuo, Wei, Wang, Liangjing
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.05.2020; Taylor & Francis Group
• Subjects: Animals; Cell Line, Tumor; Cell Movement; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - pathology; Feces - microbiology; Female; Fusobacterium nucleatum; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Keratin-7 - genetics; Keratin-7 - metabolism; KRT7-AS; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Lymphatic Metastasis; metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; NF-kappa B - metabolism; NF-κB; Research Paper/Report; RNA, Antisense - genetics; RNA, Long Noncoding - genetics; Signal Transduction; Up-Regulation; NF-κB; colorectal cancer; Fusobacterium nucleatum; metastasis; KRT7-AS
• ISSN: 1949-0976; 1949-0984
• DOI: 10.1080/19490976.2019.1695494

The enrichment of Fusobacterium nucleatum (Fn) has been identified in CRC patients and associated with worse outcomes. However, whether Fn was involved in the metastasis of CRC was not well determined. Here, we found that the abundance of Fn was significantly increased in CRC patients with lymph nodes metastasis. To further clarify the role of Fn in CRC metastasis, we performed transwell and wound healing assays after incubating CRC cell lines with or without Fn and injected Fn-treated or untreated CRC cells into nude mice via tail vein. The results indicated that Fn infection promoted CRC cells migration in vitro, as well as lung metastasis in vivo. Interestingly, colonization of Fn was detected in metastatic lung lesions of nude mice by fluorescence in situ hybridization. Mechanistically, RNA sequencing and validation study revealed that Fn significantly upregulated the expression of long non-coding RNA Keratin7-antisense (KRT7-AS) and Keratin7 (KRT7) in CRC cells. Importantly, Fn-induced CRC lung metastasis was attenuated by the depletion of KRT7-AS. In addition, KRT7-AS facilitated CRC cells migration by upregulating KRT7. Subsequently, we found that NF-κB signaling pathway was involved in the upregulation of KRT7-AS upon Fn infection. In conclusion, Fn infection upregulated KRT7-AS/KRT7 by activating NF-κB pathway, which promoted CRC cell migration in vitro and metastasis in vivo.