High Expression Of MINA Promotes Cell Proliferation And Inhibits Apoptosis In Epithelial Ovarian Cancer

Objective:To study the effect of MINA on cell proliferation,migration,cell cycle,and apoptosis in epithelial ovarian cancer,and the mechanism of MINA-regulating cell growth.Methods:1.Materials:4 normal ovarian epithelial tissues,40 epithelial ovarian cancer tissues;Human normal ovarian epithelial cell lines:IOSE-80;Human epithelial ovarian cancer cell lines:A2780,HO-8910,HEY,SKOV3.2.The MINA protein expression in EOC tissues and normal ovarian epithelial tissues was analyzed by immunohistochemistry,and MINA protein in normal ovarian epithelial cells and epithelial ovarian cancer cells was detected by Western Blotting The clinical data of patients who had epithelial ovarian cancer were collected and the relationship between MINA and clinical data was analyzed.After the expression of MINA in A2780 and HO-8910 cells was knocked down by small interfering RNA,the changes of the cell proliferation were examined by CCK8.Transwell cell migration experiment was used to examine the change in the cell migration ability after MINA was down-regulated.Changes in cell cycle and apoptosis were detected by FCM and changes in cell cycle-related and apoptosis-related proteins were detected by Western Blotting.The expression levels of H3K9mel,H3K9me2 and H3K9me3 were also detected by Western Blot.Results:1.The expression level of MINA in epithelial ovarian cancer was correlated with lymph node metastasis(P=0.042),FIGO stage(P=0.003),and the degree of cell differentiation(P=0.004),but was not significantly correlated with the age,CA125 level,and HE4 level.2.MINA protein expressed more in epithelial ovarian cancer tissues and cell lines than in normal ovarian epithelial tissues and cell line.3.After disturbing MINA expression,the ability of proliferation of epithelial ovarian cancer cells was inhibited;4.After down-regulating MINA expression,the migration capacity of epithelial ovarian cancer was interfered;5.Down-regulation of MINA caused cell cycle stagnation in G2/M,G0/G1 phase,and the expression levels of CDK2,CDK4,cyclinDl and cyclinE1 which were belonged to cell cycle-related proteins were decreased.6.Reducing MINA expression can promote apoptosis of epithelial ovarian cancer cells,and can also cause Bax protein increasing and Bcl-2 protein decreasing7.MINA regulates cell cycle and apoptosis by controlling the demineralization of H3K9me3.Conclusions:In EOC tissues and cell lines,MINA protein was highly expressed.While knock-down of MINA,cell proliferation and migration can be inhibited,cell cycle will be stagnated in G2/M,G0/G1 phase and cell apoptosis can be promoted.MINA may regulate cell cycle and apoptosis by controlling the demethylation of H3K9me3.