The Role Of Acetylation Of SMC1 In The Development Of Colon Cancer

Objective:SMC1 is a complex core component of sister chromatid cohesion adhesion^[1-4].In addition,SMC1 is involved in a variety of cellular functions,including cell survival^[5],chromosome dynamics^[6-8],cell cycle regulation^[8,9]and DNA damage repair^[9-11].Most importantly,SMC1-mediated chromosomal structural stability and DNA damage repair are considered important mechanisms for maintaining genomic integrity.Previous studies have shown that SIRT2 can deacetylate to regulate SMC1 and increase the phosphorylation level of SMC1,thereby maintaining the stability of the genome.In this paper,based on the existing research results of our research group:SIRT2 plays a role by regulating the dephosphorylation of SMC1-K579 site to increase the phosphorylation level of SMC1,and further studies the acetylation of this important site of SMC1-K579.Biological function and clinical significance.Methods:This study was divided into five parts to study the role of SMC1-K579acetylation in cell mitosis,cell proliferation,the expression of cancer tissues,the sensitivity to drugs,and whether it can act as a specific inhibitor of SIRT2.Target.1.HCT116-shSMC1 cells were used to transiently transfect WT-SMC1,K579Q-SMC1,DDK579Q-SMC1 plasmids,and immunofluorescence was used to detect the changes of multipolar and multinuclear behavior.2.CCK8 was used to detect the proliferation of shSMC1-HCT116 cells overexpressing SMC1-WT,SMC1-K579Q and SMC1-DD K579Q.3.We firstly used immunohistochemistry to detect the expression of SIRT2,SMC1-579 acetylation and SMC1-S966 phosphorylation in 68 colon cancer tissues and55 paracancerous tissues of tissue microarrays.Period correlation.Secondly,the expression of SIRT2,SMC1-579 acetylation and SMC1-S966 phosphorylation in colon cancer tissues from 230 different colon cancer tissues was detected by immunohistochemistry.4.SMC1-K579 acetylation enhances the sensitivity of cells to anticancer drugs.To further study the clinical value of SMC1-K579 acetylation,we established a xenograft model and injected HCT116shSMC1-SMC1-WT and HCT116shSMC1-SMC1-K579R stable cell lines into nude mice.When the nude mice were tumorigenic and the tumor grew to a certain size,the drug was administered,one group was injected with AGK2,and one group was injected with DMSO as a control.The size of the tumor was measured every other day and a growth curve was drawn while observing changes in body weight and making a chart.Results:1.SMC1-K579 acetylation can cause multipolar and multinuclear behavior of tumor cells,causing abnormal mitosis.2.SMC1-K579 acetylation can inhibit the proliferation of tumor cells.3.The expression of SMC1-K579 acetylation in cancer tissues is significantly lower than that in adjacent tissues.As the degree of malignancy of the tumor increases,the level of acetylation of stage IV SMC1-K579 in colon cancer is significantly higher than that of colon cancer stage I SMC1-K579.4.SMC1-K579acetylation enhances the sensitivity of cells to anticancer drugs.5.SMC1-K579 can be used as a target for SIRT2-specific inhibitors.Conclusion:This study focused on the role of SMC1-K579 acetylation in the development of colon cancer.SMC1 acetylation can cause tumor cell mitosis abnormalities,inhibit tumor cell proliferation,enhance cell sensitivity to anticancer drugs,as SIRT2 specificity Inhibitors are effective targets for inhibiting tumor proliferation.