Preliminary Study On The Role And Mechanism Of Histone Demethylation Enzyme LSD1 In The Development And Progression Of Breast Cancer

?Objective?To investigate the expression LSD1(histone lysine demethylase 1),H3K4me(Histone H3 lysine 4 monomethylation),H3K4me2(Histone H3 lysine 4 dimethylation)in breast cancer tissues and and their clinical significance.We also study the effect of phenelzine on cell growth and cell apoptosis in breast cancer MCF-7 cells line in vitro,and explore its possible mechanism.?Method?1.The expressions of LSD1,H3K4me2 and H3K4me1 in human breast cancer tissues and breast adenosis tissue were detected by immunohistochemical method.Their clinical significance and the relationship with the prognosis of the patients were explored by statistical analysis.2.After phenelzine treatments,the cell growth of MCF-7 cells MTT method,cell apoptosis was measured by TUNEL 3.Apoptosis-related proteins Bcl-2?c-myc?Caspase-3,and histone H3K4me2 were detected by western blot.?Results?1.The expression rate of LSD1 in breast cancer tissues is 58.03%(65/112,which is significantly higher than 13.33%(4/30)in breast adenosis tissue(P<0.05),It was not associated with age,tumor size,lymph node metastasis,tumor differentiation,Her-2 expression and TNM stage(P < 0.05),but was related to the expression of ER and PR,The expression rate of LSD1 in ER negative breast cancer tissues was higher than that of ER positive breast cancer tissues,and the expression rate of LSD1 in PR negative breast cancer tissues was higher than that in PR positive breast cancer tissues,with statistical significance(P<0.05).The overall survival(OS)and disease-free survival(DFS)of LSD1 positive expression group were lower than those of LSD1 negative expression group(P<0.05).2.The expression rate of H3K4me2 in breast cancer tissues is 30.36%(34/112),which is significantly lower than 83.33%(25/30)in breast adenosis tissue(P<0.05),It was not associated with age,tumor size,lymph node metastasis,tumor differentiation,Her-2 expression and TNM stage(P < 0.05),but was related to the expression of ER and PR,The expression rate of LSD1 in ER negative breast cancer tissues was lower than that of ER positive breast cancer tissues,and the expression rate of LSD1 in PR negative breast cancer tissues was lower than that in PR positive breast cancer tissues,with statistical significance(P<0.05).There was a negative correlation between the expression of LSD1 and histone H3K4me2(P=0.0002).3.The positive rate of H3K4 me in breast cancer group was 84.82%(95/112),and which is statistical significance differencethe between 93.33 %(28/30)in adenosis of breast tissues,P>0.05.4.Phenelzine inhibit the activity of LSD1 and inhibit breast cancer cell MCF-7 cell proliferation,induce cell apoptosis;The concentration 0,5,10,20?mol/Lof phenelzine treatment breast cancer MCF-7 cells after 24 h,cell proliferation rates were(100±3.11)%,(88±3.53)%,(59±4.45)%,(45±4.33)%,showed statistical significance(P<0.05);and the apoptosis rates were(3.52±1.58)%,(10.26±2.33)%,(32.62±3.62)%,(49.47±4.73)%,also showed statistical significance(P<0.05).5.Phenelzine can upregulate the level of histone H3K4me2,downregulate apoptosis inhibitory protein Bcl-2,c-myc,and upregulate expression of effector protein caspases-3?Conclusions?1.In breast cancer,LSD1 is highly expressed and H3K4me2 is low expression,They are negative correlation;The positive expression of LSD1 is a sign of bad prognosis of breast cancer,It is expected to be a new target for molecular targeted therapy of breast cancer.2 LSD1 inhibitor phenelzine can increase the level of H3K4me2,downregulate apoptosis protein Bcl-2 and c-myc,upregulate expression of effector protein caspases-3,and inhibite the proliferation of breast cancer cell MCF-7,induce apoptosis of breast cancer,is expected to become the targeted chemotherapy drugs.