Nicotinic acid suppresses liver cancer metastasis via histone lysine nicotinylation

Abstract Vitamin B3 is the major precursor of NAD+ and NADP+, however it was unknown whether this vitamin supplementation could modify histone epigenetically. Here, we report nicotinic acid (NA), a component of vitamin B3, suppresses liver cancer metastasis specifically, via stimulating histone lysine nicotinylation (Knic). Importantly, nicotinyl-CoA, that metabolically generated by NA via ACSS2, stimulates histone Knic in vivo and in vitro. Histone Knic regulates chromatin accessibility and inhibits binding of transcription factor HOXB9 to the promoter of oncogene PPFIA1, resulting in inhibition of hepatocyte carcinoma progression. Notably, we found that NA specific induces histone Knic and suppresses hepatocyte carcinoma progression, whereas nicotinamide, an amide form of nicotinic acid, does not stimulate nicotinylation, instead promotes tumour growth and metastasis. These findings suggest that vitamin B3 supplementation may contribute to cancer progression depending on its composition. Collectively, we demonstrated that histone lysine nicotinylation is a histone mark controlling gene expression and NA supresses liver cancer progression by inducing histone lysine nicotinylation.