Effect Of P53 Transcriptional Regulatory Target Gene GGT6 On Cancer

Cancer is one of the main causes of death in the world.The diagnosis and treatment of cancer and the molecular mechanism of its occurrence and development have always been an important topic in the field of life science and medicine.TP53 is a well-known tumor suppressor gene.p53 protein mainly acts as a transcription factor to regulate a variety of biological processes including apoptosis,cell cycle,DNA repair and cell proliferation through its target genes.Nutlin is a small molecule inhibitor that specifically targets MDM2/p53 interaction and activates cancer cell cycle arrest and apoptosis pathways by stabilizing p53.Nutlin is often used as an activator of p53 in biological experiments.In order to screen the target genes of p53 transcription regulation,this study performed gene differential analysis on the RNA-seq data of colorectal cancer HCT116 cells treated with Nutlin.The differential gene GGT6 was selected as a candidate target gene of p53 transcription regulation.Nutlin was added to stabilize or siRNA was transfected to knock down the expression of p53 in HCT116 and HCT8 cells.The results showed that the mRNA level of GGT6 in cells was positively correlated with the protein expression of p53.Dual luciferase reporter assay and ChIP confirmed the transcriptional regulation of GGT6 by p53.At present,there are few related studies on GGT6,and no articles have been published with GGT6 as the main research object.It is mainly screened out that GGT6 may play a role in tumors and other diseases through some omics and bioinformatics studies.The role of GGT6 in cancer was then explored.The expression of GGT6 in cancer was significantly different from that in adjacent tissues,and the overall survival of patients with high and low GGT6 expression groups was significantly different.Analysis of GGT6 expression data of TCGA colorectal cancer(CRC)and renal cancer(KIPAN)showed that GGT6 expression was higher in colorectal cancer and renal cancer tissues than in their corresponding adjacent tissues,and the overall survival time of patients with high GGT6 expression was longer than that of patients with low GGT6 expression.The difference in overall survival time was more significant in renal cancer than in colorectal cancer.Therefore,it is speculated that GGT6 is a tumor suppressor in colorectal and renal cancers.In the immune-related study of GGT6 in CRC and KIPAN patients,ssGSEA and ESTIMATE analysis showed that there was no significant difference in the infiltration of immune cells in colorectal cancer tissues between high and low expression of GGT6,while the infiltration of immune cells in renal cancer tissues with high expression of GGT6 was lower than that with low expression of GGT6.There is no significant relationship between the immune components of colorectal cancer and the prognosis of patients,while the immune components of renal cancer are significantly related to the poor prognosis of patients.Therefore,the infiltration of immune components in renal cell carcinoma a potential role in evaluating prognosis,which is not found in colorectal cancer samples.The effect of GGT6 on immune infiltration and the sensitivity of the prognosis to immune components in renal cell carcinoma patients may be an important factor for the more significant prognostic difference of GGT6 in renal cell carcinoma patients than in colorectal cancer patients.Although GGT6 belongs to the GGT family,it has not been reported to have related enzyme functions.In order to further explore the potential function of GGT6 in colorectal cancer and renal cancer,the expression of GGT6 was divided into high and low groups according to the median expression level for gene differential analysis,and functional enrichment analysis was performed on these genes.The key words "channel","transport"and "secretion" appeared very frequently in the analysis results,suggesting its potential functions in substance transport and signal transduction.GGT6 expression was positively correlated with TP53 expression in colorectal cancer,and GGT6 expression was lower in tissues with mutant TP53 than in tissues with wild-type TP53 in colon cancer.There is an important relationship between TP53 and GGT6,which are both tumor suppressor genes in colorectal cancer.