Abstract: Objective To screen out a transcriptional target gene of p53 regulation, and to analyze the role of this gene in colon adenocarcinoma(COAD) by bioinformatics.Methods RNA-seq data of colon cancer cell line HCT116 treated with p53 protein stabilizer Nutlin were analyzed for differential gene expression (DEGs) and GO, KEGG and GSEA enrichment analysis. Nutlin was treated to stabilize p53 or transfected siRNA to knock down p53 expression in HCT116 and HCT8 cells. Quantitative real-time PCR was used to detect the mRNA expression of the predicted target gene. Dual luciferase reporter assay was used to verify the transcriptional regulation of p53 on the target gene. The expression of the target gene and the prognosis of patients was analyzed by TCGA-COAD database. Results After Nutlin treatment, the genes coding for cell cycle, DNA replication and chromosome segregation etc were changed. The p53 signaling pathway was also activated. The mRNA level of GGT6 was positively correlated with the protein expression of p53 in HCT116 and HCT8 cells. Dual luciferase reporter assay identified GGT6 as a target gene of p53 transcriptional regulation. The TCGA-COAD data analysis showed that the expression of GGT6 in COAD tissues was higher than that in the adjacent tissues(P＜0.001), and the overall survival(OS) time of patients with high GGT6 expression was longer than that of patients with low GGT6 expression(P＜0.01), suggesting GGT6 as a tumor suppressor in COAD. Conclusions GGT6 is a new transcriptional target gene of p53 and a potential tumor suppressor for colon adenocarcinoma development.

Key words: p53, transcriptional regulation, GGT6, colon adenocarcinoma