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

Abstract

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