MiR-137 Targeted Regulation KDM1A/LSD1 Inhibited Lymphoma Cell Proliferation, Inducing Apoptosis

Objective: To investigate the expression level of mi R-137 in mantle cell lymphoma cell,verification mi R-137 regulation of KDM1A/LSD1 gene and study the effect of overexpression of mi R-137 on cell proliferation, apoptosis and histone methylation in mantle cell lymphoma(MCL) Jeko-1 cells.Methods:1.The difference expression of mi R-137 in the cell lymphoma cell line and normal mononuclear cells by RQ-PCR. 2. Mi R-137 being KDM1A/LSD1 Target gene is verified by the dual luciferase report KDM1A/LSD1. 3.Mi R-137 mimics was designed in commocially and transfected into Jeko-1 cells by LipofectamineTM2000. Cell growth was detetced by MTT. Cell apoptosis was measured by Flow cytometry. The expression of apoptosis related proteins Bcl-2、Bax、Caspase-3、Caspase-9 and the expression of LSD1 protein、histone methylation of H3K4 was detected by Western Blot.Results: 1. The mi R-137 expression level in sp49、Mino、Jeko cell lines respectively was: 0.0360 + 0.0076, 0.0173 + 0.0029, 0.0151 + 0.0024; while in the control group(mononuclear cells in five blood donors)was 0. 425 + 0.0167 by RQ-PCR. The difference was statistically significant in each lymph tumor cell lines and the control group,p<0.05.2. KDM1A/LSD1 3 ’UTR luciferase can be regulated by mi R-137(p=0.0352), the combination site in mi R-137 is located in the mutation position 65-71.3. Overexpression of mi R-137 mimics inhibited cells proliferation and induced cell apoptosis in Jeko-1 cell line. After 24 h transfection,cell apoptosis was(1.89 + 0.32)%,(3.12 + 1.75)%,(44.76 + 3.58)% in mimics control group, NC group, mi R-137 mimics group, p<0.05. Mi R-137 mimic downregulated Bcl-2 and upregulated Bax, Caspase-3, caspase-9. It inhibited LSD1, and promoted H3K4me1, H3K4me2 methylation. But variation of H3K4me3 was not seen.Conclusions: Mi R-137 showed low expression in the cell line of mantle cell lymphoma.KDM1A/LSD1 is the downstream genes of mi R-137. Overexpression of mi R-137 inhibits cell proliferation, induce cell apoptosis. Mi R-137 upregulates H3K4me1, H3K4me2 methylation, It might be the target of MCL therqpy.