Relationship between Fusobacterium nucleatum, inflammatory mediators and microRNAs in colorectal carcinogenesis

Figure 5 Representation illustrating the interactions of Fusobacterium nucleatum in colorectal cancer. Fusobacterium nucleatum (F. nucleatum) presents the virulence factors FadA and Fap2 and lipopolysaccharide (LPS), which are recognized by Toll-like receptors (TLR2 and TLR4) mediating F. nucleatum invasion and the promotion of colorectal cancer (CRC). FadA, a surface adhesion protein, can bind to E-cadherin on CRC cells, activating B-catenin signalling. Fap2, a galactose-sensitive haemagglutinin and adhesion protein binding to Gal-GalNAc, contributes to the invasive ability of F. nucleatum. The TLR2/TLR4/MYD88 pathway is activated in response to F. nucleatum, leading to the activation of NF-κB, a transcription factor that is involved in regulating the expression of many genes, leading to elevated expression levels of oncogenes and pro-inflammatory cytokines, mainly interleukin (IL)1B, IL6, IL8 and tumour necrosis factor, inducing the production of reactive oxygen species, which subsequently lead to inflammation and DNA damage that promotes tumour growth and progression. Furthermore, these pathways may be under the regulation of differentially expressed microRNAs. ROS: Reactive oxygen species; TNF: Tumour necrosis factor; IL: Interleukin; NF-κB: Nuclear factor kappa B; TLR: Toll-like receptor; miRNA: MicroRNA.