文章：

miR-203和miR-221调控原发性血小板增多症中的SOCS1和SOCS3

miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia

原文发布日期：2016-03-18

DOI: 10.1038/bcj.2016.10

类型: Original Article

开放获取: 是

英文摘要：

The biological basis of essential thrombocythemia (ET) patients lacking known mutations is still unknown. MicroRNAs (miRNA) regulate hematopoietic differentiation and are deregulated in several hematopoietic malignancies. However, miRNA expression in ET patients has been poorly explored. We performed miRNA profiling in platelets from 19 ET patients and 10 healthy controls. Hierarchical cluster analysis showed two well-separated clusters between patients and controls, indicating that ET platelets had a characteristic 70-miRNA signature (P<0.0001), 68 of which were downregulated. According to the mutational status, three differentially expressed miRNAs, miR-15a (P=0.045), miR-150 (P=0.001) and miR-519a (P=0.036), were identified. A 40-miRNA signature was identified characterizing JAK2V617F-positive ET patients. Eight genes, whose interaction with the miRNAs could activate the JAK/STAT pathway were identified. An inverse correlation was observed between miRNAs expression and their target genes for SOCS1 and miR-221, SOCS3 and miR-221, SOCS3 and miR-203, and PTPN11 and miR-23a. All three miRNAs were upregulated in JAK2V617F-negative ET patients. SOCS1 and SOCS3 were validated as targets of miR-221 and miR-203, respectively. In summary, our study shows that platelets from JAK2V617F-negative ET patients harbor a specific miRNA signature that can participate in the modulation of the JAK/STAT pathway through regulation of key genes as SOCS1 and SOCS3.

摘要翻译： 

缺乏已知突变原发性血小板增多症（ET）患者的生物学基础仍不明确。MicroRNA（miRNA）在造血分化中起调控作用，并在多种造血系统恶性肿瘤中出现失调。然而，关于ET患者miRNA表达的研究尚不充分。我们对19例ET患者和10例健康对照者的血小板进行了miRNA谱分析。层次聚类分析显示患者与对照组形成两个明显分离的聚类，表明ET血小板具有包含70个miRNA的特征性表达谱（P<0.0001），其中68个呈下调表达。根据突变状态，我们鉴定出三个差异表达的miRNA：miR-15a（P=0.045）、miR-150（P=0.001）和miR-519a（P=0.036）。研究还发现JAK2V617F阳性ET患者具有包含40个miRNA的特征性表达谱。我们确定了8个能与miRNA相互作用激活JAK/STAT通路的关键基因，并观察到SOCS1与miR-221、SOCS3与miR-221、SOCS3与miR-203以及PTPN11与miR-23a之间存在表达负相关性。所有这三个miRNA在JAK2V617F阴性ET患者中均呈上调表达。实验验证SOCS1和SOCS3分别是miR-221和miR-203的靶基因。本研究首次揭示JAK2V617F阴性ET患者的血小板携带特异性miRNA表达谱，该特征谱可能通过调控SOCS1、SOCS3等关键基因参与JAK/STAT通路的调节。

原文链接：

miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia