Abstract: Objective To investigate the role and mechanism of lysine acetyltransferase 8(KAT8) on the proliferation of colorectal cancer cells. Methods The expression of KAT8 in cancerous tissues and adjacent tissues of colorectal cancer patients was analyzed by RNA-seq data of TCGA database. Cell proliferation was detected by colony-forming unit assays and CCK8. The GEO database was used to analyze the differential genes of KAT8 knockdown cells and control cells and perform functional pathway enrichment analysis. In the colorectal cancer database hosted on cBioPortal, that conducted an analysis examining the correlation between KAT8 and genes in the regulation of N6-methyladenosine(m6A) modification. Western blot technique was employed to assess the protein expression levels of KAT8 and METTL3. Results Compared to human normal colorectal tissue, KAT8 was highly expressed in colorectal cancer(P＜0.05). Knockdown or selective inactivation of KAT8 inhibited colorectal cancer cells proliferation (P＜0.05). In colorectal cancer cell lines, knocking down KAT8 reduced m6A modification levels (P＜0.05). Knocking down KAT8 inhibited METTL3 expression (P＜0.05). Over-expression of METTL3 reversed cell proliferation which was inhibited by knockdown KAT8(P＜0.05). Conclusions KAT8 facilitates the proliferation of colorectal cancer cell lines through regulation of METTL3-mediated m6A modifications.

Key words: KAT8, METTL3, N6-methyladenosion, cell proliferation