Over-expression of miR-196b-5p is significantly associated with the progression of myelodysplastic syndrome
Over-expression of miR-196b-5p is significantly associated with the progression of myelodysplastic syndrome
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miR-196b-5p 的过表达与骨髓增生异常综合征的进展显着相关
DOI：
10.1007/s12185-017-2201-9
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发表时间：
2017-06-01
影响因子：
2.1
通讯作者：
Liu, Zhenfang
中科院分区：
文献类型：
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作者：
Wen, Jing;Huang, Ying;Liu, Zhenfang
骨髓增生异常综合征（MDS）是一种克隆性干细胞疾病，其特征是无效的造血，具有转化为急性髓细胞白血病（AML）的高风险。miRNA在多种癌症中作为肿瘤抑制因子和癌基因发挥作用，并调节造血干细胞和祖细胞（HSPC）的分化潜能。研究表明，miRNAs在MDS的发生发展中可能起重要作用。我们根据国际预后评分系统（IPSS）指示的不同风险分层分析了从MDS患者收集的骨髓样本。我们证明，与健康对照相比，miR-196 b-5 p在中间II和更高的组中上调，特别是在继发性AML（s-AML）患者中（P< 0.01），表明更高的表达水平与MDS发展的风险增加相关。我们观察到用miR-196- 5 p模拟物或抑制剂转染后MDS-L细胞增殖和凋亡的变化。上调miR-196 b-5 p表达后，MDS-L细胞增殖能力增强，凋亡能力减弱（P< 0.05）。与此相反，下调miR-196 b-5 p表达可降低细胞增殖，增加细胞凋亡（P< 0.05）。我们的结论是，miR-196 b-5 p的过度表达可能与MDS患者转化为白血病的风险密切相关。
Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis with a high risk of transformation to acute myeloid leukemia (AML). miRNAs function as tumor suppressors and oncogenes in various cancers and regulate the differentiation potential of hematopoietic stem and progenitor cells (HSPCs). It has been suggested that miRNAs may play an important role in progression of MDS. We analyzed bone marrow samples collected from MDS patients according to different risk stratification indicated by the International Prognostic Scoring System (IPSS). We demonstrated that miR-196b-5p was up-regulated in intermediate II and higher groups, and in secondary AML (s-AML) patients in particular (P< 0.01) compared with healthy controls, suggesting that the higher expression levels are associated with increased risk of the development of MDS. We observed changes in proliferation and apoptosis in MDS-L cells following transfection with miR-196-5p mimics or inhibitors. After up-regulating the expression of miR-196b-5p, proliferation of MDS-L cells was up-regulated, whereas apoptosis was down-regulated (P< 0.05). In contrast, down-regulation of miR-196b-5p expression decreased cell proliferation and increased apoptosis (P< 0.05). We concluded that over-expression of miR-196b-5p may be closely associated with the risk of transformation to leukemia in MDS patients.