OBJECTIVE: Acute lymphocytic leukemia (ALL) is a multi-factorial blood disease with unknown pathogenesis. Histone H3K4 methylation was significantly reduced in ALL patients, whereas jumonji AT-rich interactive domain 1B (JARID1B) was the specific demethylase of H3K4me. This study explores the expression level of JARID1B in ALL patients and down-regulated JARID1B expression in ALL cells to explore the function of JARID1B in ALL.
PATIENTS AND METHODS: JARID1B mRNA expression level in ALL patients was detected by Real-time PCR. The peripheral blood mononuclear cells from healthy volunteers were selected as control. JARID1B shRNA was transfected with MOLT-4 cells and BALL-1 cells. JARID1B protein expression and H3K4me2 and H3K4me3 levels were detected by Western blot assay. Cell proliferation was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis and cell cycle were determined by flow cytometry. Bcl-2, Bax, Procaspase 3, and cyclin P21 expressions were evaluated by Western blot assay.
RESULTS: JARID1B mRNA expression in primary bone marrow cells from ALL patients was significantly higher than that of healthy volunteers (p<0.05). The levels of histone H3K4me3 and H3K4me2 were up-regulated after JARID1B shRNA transfection. JARID1B shRNA significantly inhibited the proliferation of MOLT-4 and BALL-1 cells, induced apoptosis, and blocked cell cycle in G0/G1 phase compared with the control group (p<0.05).
CONCLUSIONS: JARID1B is highly expressed in ALL. Down-regulating its expression inhibited leukemia cell proliferation, promoted apoptosis, and blocked cell cycle in G0/G1 phase through histone H3K4 methylation. JARID1B is an oncogene in ALL.Free PDF Download
To cite this article
Y.-Q. Huang, Y. Zou, R.-J. Zheng, X.-D. Ma
Down-regulation of JARID1B expression inhibits cell proliferation, induces apoptosis and blocks cell cycle in human acute lymphoblastic leukemia cells
Eur Rev Med Pharmacol Sci
Vol. 22 - N. 5