The Effect Of Histone Methyltransferase SETDB1 In The Proliferation And Apoptosis Of Esophageal Cancer

PurposeEsophageal cancer is one of the most common malignant gastrointestinal cancers with high mortality and poor prognosis,it is expected that the next 10 years will become an increasingly serious health problem.In recent years,with the development of medicine,although some advances have been made in the diagnosis and treatment of esophageal cancer,the mortality rate of esophageal cancer remains high.The main reason is that the early symptoms of esophageal cancer are not typical,when the severity of severe symptoms of varying duration,or even without any symptoms,easily overlooked.Therefore,in order to improve the rate of diagnosis and treatment of patients with esophageal cancer,reduce mortality and improve the quality of life of patients,we need to find effective molecular biology targets for the diagnosis of esophageal cancer,and further study the molecular mechanisms of esophageal cancer development to achieve the purpose of accurately determining early esophageal cancer,and make effective judgments on esophageal cancer invasion,metastasis,recurrence,etc.The SETDB1 gene encodes a histone methyltransferase that maps to human chromosome 1q21 and is widely expressed in mammalian tissue cells.The study found that SETDB1 is closely related to the proliferation,apoptosis and other biological behaviors of tumor cells and the prognosis of patients,and has been established as an oncogene of human lung cancer,melanoma and renal tumor.Therefore,SETDB1 is considered to be a biological marker with potential application of tumor markers and prognostic evaluation.Histone methylation transferase is mainly involved in the process of histone methylation and plays an important role in the growth and evolution of tumors.Therefore,it is of great significance to study the function and mechanism of histone methyltransferase.Current studies have shown that SETDB1 plays an important role in embryonic development in mice and is particularly evident in the nervous system.The histone methyltransferase SETDB1 is mainly involved in the methylation of H3K9me3 and plays an important role in tumor proliferation and apoptosis.However,the role of SETDB1 in esophageal cancer has not yet been elucidated and there is no relevant data confirming its expression in esophageal cancer tissues or cell lines.Here,we initially explored the role of SETDB1 in the proliferation and apoptosis of esophageal cancer.The subject firstly used immunohistochemistry to detect the expression of SETDB1 in esophageal cancer patients.At the same time,we analyzed the correlation between clinical pathological parameters and the existence of their expression.Then we used siRNA interference technology to silence the SETDB1 gene in esophageal cancer cells,to make it low expression,analysis and judgement of the low expression of histone methyltransferase SETDB1 onthe proliferation and apoptosis of esophageal cancer cells.Methods1.The expression and clinical significance of SETDB1 in esophageal cancer.Immunohistochemistry was used to detect the expression of SETDB1 in44 cases of esophageal cancer tissue and 36 adjacent tissues.The results showed that the expression of SETDB1 in esophageal cancer tissues was higher than that in adjacent tissues without invasion of tumors.The difference was statistically significant(P <0.01).The high expression of SETDB1 was associated with tumor lymph node metastasis,and some tumors were not metastasized to low expression.The difference was statistically significant(P<0.05).There was no significant correlation with the patient’s age,gender,tumor size,depth of invasion,and differentiation(P>0.05).2.The effect of silencing SETDB1 on proliferation and apoptosis of esophageal cancer cells.1)The histone methyltransferase SETDB1 is expressed in esophageal cancer cells KYSE150 and EC9706,and the expression level is relatively high in esophageal cancer cell line EC9706.2)Two synthetic fragments of histone methyltransferase SETDB1 siRNA,the efficiency of SETDB1/siRNA-2/-3 interference was comparable and both were lower than those of the control group SETDB1/NC.3)The results of CCK8 showed that after silencing SETDB1 gene,theproliferation of esophageal cancer EC9706/SETDB1/siRNA-2/-3 cells was lower than that of the control group EC9706/NC.4)The results of qRT-PCR and Western blot showed that the expression of Bcl-2 gene and CyclinD1 gene were decreased,and the expression of Bax mRNA and protein was increased.ConclusionSETDB1 was highly expressed in esophageal cancer tissues.The high expression of SETDB1 was associated with tumor lymph node metastasis.Some tumors that had not metastasized showed low expression.In vitro experiments demonstrated that the proliferation and apoptosis of esophageal cancer cell lines were regulated by the histone methyltransferase SETDB1 gene.Silencing the SETDB1 gene can effectively inhibit the proliferation of esophageal cancer cells and promote their apoptosis.