Epigenetic Regualtion The Expression Of DKK2 And Molecular Mechanism For Its Supperssive Effects On Cellgrowth And Migration In Colon Cancer

Cancer is a major public health problem around the world and is one of the most common fatal diseases.As is shown in the National Cancer Center statistics in 2017: the incidence and mortality of colon cancer in the United States were among the top three [1].In developing countries,the incidence and mortality of cancer is much higher than that of developed countries.According to the China cancer data published in American CA CANCER J CLIN 2016[2]: the incidence and death rate of cancer patients in China were on rising.In 2015,about 281400 patients died of cancer,with an average of 7500 patients every day.Colon cancer was the most common digestive malignant tumors.Although the improvement of living standard,the morbidity and mortality rate were still increasing.Therefore,it is of great significance to find a new treatment for the treatment and prevention of cancer.The Dickkopf(DKK)-related protein family is composed of four secreted glycoproteins,DKK1 through DKK4.The DKK2 gene is located at 4q25,a commonly-deleted tumor suppressive locus in multiple tumors.In the curruent literature,although epigenetic silencing of DKK2 by promoter methylation has been observed in several tumors[3-4],its biological functions and related molecular mechanisms in CRC have not been elucidated[5-6].Thus we speculate that DKK2 may be involved as a tumor suppressor gene in the carcinogenesis and progression of colon cancer.In this study,we examined the expression of DKK2 in colon tumor cell lines by RT-PCR and its promoter methylation status in colon tumor cell lines and primary tumors by MSP.To investigate the function of DKK2,colony formation,cell proliferation,flow cytometric analyses of the cell cycle and apoptosis,wound healing,transwell,tumor growth in vivo was used.The results showed that: methylation of the DKK2 promoter was observed in all of these cell lines,which was consistent with the low expression or silencing of DKK2.pharmaceutical demethylation restored DKK2 expression in all three cell lines,along with an increase in unmethylated promoter alleles in HT-29 cell lines.Ectopic expression of DKK2 inhibited colony formation and cell viability by inducing cell cycle G0/G1 arrest and apoptosis,and growth of stable DKK2-infected HCT116 cells in nude mice was decreased compared to controls.Our data further showed that restoration of DKK2 expression resulted in downregulation expression of active β-catenin and its downstream target genes In summary,DKK2 as a tumor suppressor gene involved in the development of colon cancer,colon cancer may be the early diagnosis and treatment of the relevant molecular basis.