microRNA-452 exerts growth-suppressive activity against T-cell acute lymphoblastic leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored. It was found that miR-452 expression levels were significantly lower in T-ALL specimens than in normal lymph node biopsies (P=0.0079). T-ALL specimens had a significantly higher methylation level in the promoter of miR-452 than normal lymph node tissues (P=0.0014). Consistently, miR-452 was downregulated in Jurkat and Molt-4 T-ALL cells, whose expression was restored after treatment with a demethylation agent 5-aza-2'-deoxycytidine. Ectopic expression of miR-452 inhibited the proliferation of Jurkat and Molt-4 cells and induced a G0/G1 cell cycle arrest. Overexpression of miR-452 suppressed the protein expression of BMI1 in T-ALL cells. Rescue experiments revealed that overexpression of BMI1 partially reversed the growth-suppressive effect of miR-452 on T-ALL cells. Xenograft tumor studies confirmed that overexpression of miR-452 suppressed tumor growth in nude mice and reduced the expression of BMI1. Collectively, miR-452 is epigenetically silenced and targets BMI1 to exert a growth suppressive activity in T-ALL. Restoration of miR-452 expression may represent a promising therapeutic strategy for this malignancy.
['Wang|Haihao|H|', 'Guo|Qiannan|Q|', 'Zhu|Guizhi|G|', 'Zhu|Shuo|S|', 'Yang|Peiwen|P|', 'Zhang|Mingsheng|M|']
D000328:Adult D000368:Aged D000818:Animals D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D049109:Cell Proliferation D015536:Down-Regulation D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D008875:Middle Aged D063150:Polycomb Repressive Complex 1 D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma D023041:Xenograft Model Antitumor Assays D055815:Young Adult
cell cycle