Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis: down-regulation of micro RNA-1 and -133a.

Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis: down-regulation of micro RNA-1 and -133a.
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DOI:
10.1186/1479-5876-7-39
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发表时间:
2009-06-04
影响因子:
7.4
通讯作者:
Stroncek D
Stroncek D
中科院分区:
医学2区
文献类型:
--
作者:
Slezak S;Jin P;Caruccio L;Ren J;Bennett M;Zia N;Adams S;Wang E;Ascensao J;Schechter G;Stroncek D

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由于 JAK2 中的 V617F 突变可能不是骨髓谱疾病 (MPD) 的起始事件,我们将真性红细胞增多症 (PV) 和原发性血小板增多症 (ET) 患者的中性粒细胞、G-CSF 给药刺激的中性粒细胞和正常未刺激的中性粒细胞的分子变化进行了比较。使用 827 个探针评估 6 名 MPD 患者的中性粒细胞; 4 名接受 PV,2 名接受 ET,5 名健康受试者和 6 名健康受试者接受 G-CSF。此外,通过流式细胞术分析中性粒细胞抗原表达,通过ELISA分析64种血清蛋白水平。 MPD 患者的中性粒细胞基因表达谱与健康受试者(无论是未刺激的还是 G-CSF 动员的)相似但不同。 MPD 中性粒细胞中的差异表达基因更可能位于与炎症有关的途径中,而 G-CSF 动员的中性粒细胞中的差异表达基因更可能属于代谢途径。在 MPD 中性粒细胞中,CCR1 的表达增加,而一些 NF-κB 通路基因的表达减少。 MPD 中性粒细胞中的 MicroRNA miR-133a 和 miR-1 下调最多。 MPD 患者中 11 种血清蛋白水平升高,包括 MMP-10、MMP-13、VCAM、P-选择素、PDGF-BB 和 CCR1 配体 MIP-1α。这些研究表明,特别参与炎症通路(包括 NF-κB 通路)的基因存在差异表达,并且 miR-133a 和 miR-1 下调。这两种 microRNA 先前已被认为与某些癌症以及心肌细胞和骨骼肌细胞肥大的调节有关。这些变化可能导致 MPD 的临床表现。
Since the V617F mutation in JAK2 may not be the initiating event in myeloprofilerative disorders (MPDs) we compared molecular changes in neutrophils from patients with polycythemia vera (PV) and essential thrombocythosis (ET), to neutrophils stimulated by G-CSF administration and to normal unstimulated neutrophils A gene expression oligonucleotide microarray with more than 35,000 probes and a microRNA (miR) expression array with 827 probes were used to assess neutrophils from 6 MPD patients; 4 with PV and 2 with ET, 5 healthy subjects and 6 healthy subjects given G-CSF. In addition, neutrophil antigen expression was analyzed by flow cytometry and 64 serum protein levels were analyzed by ELISA. Gene expression profiles of neutrophils from the MPD patients were similar but distinct from those of healthy subjects, either unstimulated or G-CSF-mobilized. The differentially expressed genes in MPD neutrophils were more likely to be in pathways involved with inflammation while those of G-CSF-mobilized neutrophils were more likely to belong to metabolic pathways. In MPD neutrophils the expression of CCR1 was increased and that of several NF-κB pathway genes were decreased. MicroRNA miR-133a and miR-1 in MPD neutrophils were down-regulated the most. Levels of 11 serum proteins were increased in MPD patients including MMP-10, MMP-13, VCAM, P-selectin, PDGF-BB and a CCR1 ligand, MIP-1α. These studies showed differential expression of genes particularly involved in inflammatory pathways including the NF-κB pathway and down-regulation of miR-133a and miR-1. These two microRNAs have been previous associated with certain cancers as well as the regulation of hyperthrophy of cardiac and skeletal muscle cells. These changes may contribute to the clinical manifestations of the MPDs.
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发表时间: 2008-07-01
期刊: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
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发表时间: 2001-12-01
期刊: BLOOD
影响因子: 20.3
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DOI: 10.1158/0008-5472.can-05-3433
发表时间: 2006-03-15
期刊: CANCER RESEARCH
影响因子: 11.2
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