Objective To explore the association of peroxisome proliferators-activated receptor-γ coactivator-1 (PPARGC1) Gly482Ser with apolipoprotein E (ApoE) variations in longevity (aged above 90 yrs) Hans in Guangxi Yongfu and to explore the potential association between the variations and metabolic traits.Methods Based on our survey in Guangxi Yongfu in 2008-2011,212 elderly cases (aged 90～105 years) were included as longevity group and 207 cases without longevity history were included as control group.By household survey,we collected the longevity related parameters,blood glucose,blood lipid,blood pressure and other related metabolic traits.Peripheral blood was collected to extract DNA,the gene variations of Gly482Ser and ApoE were genotyped,and the database with genome and traits information were set up.By univariate analysis and multivariate genetic statistical analysis,the association between the variations and longevity and metabolic traits was assessed.Results Compared with the control group,the levels of fasting blood glucose,total cholesterol and low density lipoprotein were lower in the longevity group.Gly482Ser was genotyped in all samples and fully fulfilled the Hardy Weinberg equilibrium.After the Bonferroni correction,recessive model failed to find association between GG genotype and longevity.Stratified analyses by ApoEε4 allele revealed that,in the subgroup with no ApoEε4,PPARGC-1 GG genotype was positively associated with longevity in the recessive model,even after Bonferroni correction (OR =1.72,P＜0.05).In addition,longevity group with Gly482Ser GG genotype seemed to have relativelower fasting blood glucose (P ＜ 0.05) and higher high density lipoprotein levels (P ＜ 0.05).Conclusions Longevity Hans in Guangxi Yongfu preserve better metabolic state compared with the control group.GG genotype of Gly482Ser in PPARGC-1 is positively associated with longevity,which depends on not carrying the risk allele of ApoE ε4.

Objective To investigate the role and mechanism of lysine acetyltransferase 8(KAT8)on the prolifera-tion of colorectal cancer cells.Methods The expression of KAT8 in cancerous tissues and adjacent tissues of color-ectal 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 lev-els 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 prolifera-tion(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 prolifera-tion which was inhibited by knockdown KAT8(P＜0.05).Conclusions KAT8 facilitates the proliferation of color-ectal cancer cell lines through regulation of METTL3-mediated m6A modifications.