去甲基化治疗对骨髓增生异常综合征患者microRNA-124表达的激活作用

Reactivated Expression of MicroRNA-124 in Patients with Myelodysplastic Syndromes after Demethylating Therapy

目的:通过检测microRNA-124(miR-124)在MDS患者骨髓细胞中的表达水平及在地西他滨治疗前后的表达变化,探讨miR-124在MDS发病中的作用及表达调控机制。方法:采用茎环法实时荧光定量聚合酶链反应检测35例MDS患者骨髓单个核细胞中miR-124的表达水平,同步检测10例正常供者骨髓中miR-124表达水平作为对照组。结果:MDS患者的miR-124表达水平低于正常对照组。低危组(包括RA和RCMD亚型)与正常对照组比较,差异无统计学意义(P>0.05),但高危组(包括RAEB1、RAEB2和CMML亚型)miR-124表达水平与正常对照组比较有统计学差异,前者miR-124中位数明显低于后者(P<0.01)。对18例MDS患者应用小剂量地西他滨治疗前后的miR-124表达水平检测发现,7例治疗后miR-124表达水平升高,差异有统计学意义(P<0.05)。此结果说明去甲基化可激活该基因的表达。结论:miR-124基因过度甲基化和表达沉默可能是诱发MDS患者细胞克隆性转化的重要因素。

Objective：To explore the role of microRNA-124（miR-124） in the pathogenesis of myelodysplastic syndromes（MDS） through detecting the expression level of miR-124 in bone marrow mononuclear cells（MNC） of MDS patients before and after demethylating therapy with decitabine.Methods：The expression levels of miR-124 in the MNC of 35 MDS patients and 10 healthy donors were detected with stem-loop quantitative real time polymerase chain reaction assay.Results：The expression level of miR-124 was lower in MDS patients than that in healthy donors.The difference was not statistically significant between patients with low-risk MDS subtypes（RA and RCMD） and control,but statistically significant between patients with high-risk MDS subtypes（RAEB1,RAEB2 and CMML） and control.This study also proved that expression of miR-124 was reactivated in 7 out of 18 MDS patients after treatment with low dose decitabine.Conclusion：The hypermethylation and silencing of miR-124 may be an important factor in the clonal transformation of MDS cells.