Methylation status of microRNA gene let-7a-3 in acute myeloid leukemia patients
Date Issued
2008
Date
2008
Author(s)
Chen, Yong-Sian
Abstract
Let-7 family miRNAs repress several genes involved in cell cycle, including RAS and HMGA2 . By this way, they play specific roles in cell proliferation, differentiation and the other biological processes. Let-7a-3 belongs to the archetypal let-7 miRNA gene family and was found to be regulated by epigenetic regulation. Recent study showed that let-7a-3 was methylated in epithelial ovarian cancer and methylation status was associated with survival of patients. In this study, we speculate the methylation status of let-7a-3 and its significance in acute myeloid leukemia.ombined bisulfite restriction analysis(COBRA)were used to evaluate the let-7a-3 methylation status in 90 AML patients. We found that let-7a-3 was methylated in 73 patients(81.1%), partial methylated in 11 patients(12.2%)and unmethylated in 6 patients(6.7%). Of them, 16 patients were simultaneously analyzed for methylation status of 33 CpG sites in let-7a-3 promoter region by using bisulfite sequencing PCR method (BSSP). BSSP demonstrated similar results to the COBRA method, showing the methylation levels ranged from 56% to 86% in patients with let-7a-3 methylated, 45% to 58% in patients with let-7a-3 partial methylated and 12% to 15% in patients with let-7a-3 unmethylated. hi-square test was performed to assess the association of let-7a-3 methylation status with patients’ age, gender and FAB subtype . We found that let-7a-3 methylation status was negatively correlated with karyotype and CEBPA methylation significantly(0.006 and 0.002, respectively). Kaplan-Meier survival analysis showed that let-7a-3 methylation in AML patients with intermediate karyotype or CEBPA unmethylation had better prognosis.
Subjects
microRNA
let-7a-3
methylation
Acute myeloid leukemia
SDGs
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