Both endogenous and exogenous miR-139–5p inhibit Fusobacterium nucleatum-related colorectal cancer development

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Colorectal carcinogenesis represents a heterogeneous process which influenced by diet, environmental and microbial exposures. Microbes in the gut might take up microRNAs (miRNAs) and these miRNAs might affect microbes in turn. Our previous work identified miR-139–5p as a tumor suppressor gene down-regulated in CRC. At present, the regulatory role and mechanism of miR-139–5p between Fusobacterium nucleatum and CRC are unclear. In this study, after co-incubating Fusobacterium nucleatum with CRC cells, MTT assay, colony formation assay and wound-healing assay showed that Fusobacterium nucleatum could stimulate cell proliferation and migration. After knocking down the expression of c-met in cells, western blot assay proved that knocking down c-met could weaken this stimulation. C-met is one of the target genes of miR-139–5p. Experimented with miR-139–5p overexpressed CRC cell lines, we found the same results as knocking down c-met, which means that endogenous miR-139–5p can reduce the stimulation. Next, by co-incubating the exogenous miR-139–5p mimics with Fusobacterium nucleatum, we proved that exogenous miR-139–5p could inhibit the proliferation of Fusobacterium nucleatum. After treating CRC cells with Fusobacterium nucleatum, which incubated with miR-139–5p mimics in advance, MTT assay indicated that the stimulation of Fusobacterium nucleatum was weakened. Besides, we speculated the binding site between miR-139–5p and Fusobacterium nucleatum. In sum, our study suggests a new prospect for the treatment of CRC, and the combination of Fusobacterium nucleatum and miR-139–5p could be used as a more valuable comprehensive biomarker for CRC prognosis.