Effect Of G9a On Proliferation And Apoptosis In Gastric Cancer Cells

Objective and Significance:Gastric cancer has a high morbidity and mortality in the world,especially in east Asian countries.Because the early detection rate is low,and because the early stage of the tumoris prone to invasion lymphatic and blood.Most of the cases have developed to the middle or late stage gastric cancer with poor prognosis.With the development of molecular biology,the regulation of epigenetics in tumor has attracted much attention.Histone lysine methyltransferase G9 a can catalyze single,double and trimethylation of histone H3K9.It plays a positive regulatory role in avariety of tumors and is closely related to biological functions such as proliferation,invasion and metastasis of tumors.However,the role of G9 a in gastric cancer cells has rarely been reported.This study attempts to reveal the expression level of G9 a in gastric cancer tissues and its correlation with prognosis.On this basis,specific G9a-targeted small molecule inhibitor will applie to interfere with the biological activity of G9 a,so as to observe the changes in the proliferation,apoptosis and other biological behaviors of gastric cancer cells,in order to reveal the molecular mechanism of G9 a regulating gastric cancer cells.Research Methods:The difference in G9 a expression in gastric cancer tissues and adjacent tissues were analyzed from the Oncomine and the correlation between G9 a expression level and prognosis were analyzed from the kaplan-meier Plotter data bases.Human gastric cancer cell lines SGC-7901 and MKN-45 were selected as experimental objects to detect the expression level of G9 a in gastric cancer cells by Western Blot.Gastric cancer cells were treated with BIX01294,a small molecule inhibitor specifically targeting G9 a,to observe the morphological changes,CCK-8 assay and colony formation assay were used to detect the proliferation and clonal formation of gastric cancer.Finnally,Flow Cytometry was used to detect the apoptosis of gastric cancer cells treated with small molecule inhibitor BIX01294.Results:G9a is highly expressed in gastric cancer(P<0.01),and the high expression of G9 a indicates poor prognosis(P<0.01).G9 a were highly expressed in human gastric cancer cell lines both SGC-7901 and MKN-45.After the application of BIX01294,a small molecule inhibitors pecifically targeting G9 a,the volume of gastric cancer cells were decreased,the intercellular connections were disappeared,and the cells were shriveled,became round and fell off,which were the characteristics of a poptosis.The inhibitor BIX01294 has a significant inhibitory effect on the proliferation and cell colony formation of gastric cancer cells(all P<0.05).Flow Cytometry results showed that inhibitor BIX01294 can promote apoptosis of gastric cancer cells(P<0.05)Conclusion and Significance:Histone methyltransferase G9 a is highly expressed in gastric cancer tissues,and the high level of G9 a expression is positively correlated with poor prognosis of gastric cancer.The application of BIX01294,a small molecule inhibitor specifically targeting G9 a,can significantly inhibit the proliferation and clonal proliferation of gastric cancer cells and promote their apoptosis...