Epigenetic regulation of reelin expression in multiple myeloma

Epigenetic regulation of reelin expression in multiple myeloma
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多发性骨髓瘤中 reelin 表达的表观遗传调控。

DOI:
10.1002/hon.2311
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发表时间:
2017-12-01
影响因子:
3.3
通讯作者:
Ge, Qing
Ge, Qing
中科院分区:
医学4区
文献类型:
--
作者:
Lin, Liang;Wang, Pingzhang;Ge, Qing

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Reelin(REIN)是一种分泌的细胞外基质糖蛋白,与神经元细胞和少数类型的非神经元细胞的定位和迁移相关。我们以前报道过REIN在多发性骨髓瘤细胞中的表达。高表达的CD 45 N与预后不良和增强的骨髓瘤细胞粘附和存活相关。为了检查CD 3 N表达的表观遗传调节,分析了其在骨髓瘤衍生的细胞系和来自骨髓瘤患者的原发性肿瘤细胞中的启动子甲基化状态。CD 19(+)B细胞中CD 13 N表达中等,而CD 138(+)浆细胞中CD 13 N表达上调。在多发性骨髓瘤细胞中发现了进一步上调的cDNAN转录。在骨髓瘤细胞系和患者中,HSP 7 N的高表达与HSP 7 N启动子区的低甲基化有关。去甲基化增加体外转录。总之,我们确定了启动子近端胞嘧啶-磷酸-鸟嘌呤二核苷酸的甲基化状态决定了骨髓瘤细胞中CD 3 N的表达。版权所有(C)2016约翰威利父子有限公司
Reelin (REIN) is a secreted extracellular matrix glycoprotein associated with the positioning and migration of neuronal cells and a few types of non-neuronal cells. We have previously reported REIN expression in multiple myeloma cells. High RELN expression was associated with poor prognosis and enhanced myeloma cell adhesion and survival. To examine the epigenetic regulation of RELN expression, its promoter methylation status in myeloma-derived cell lines and primary tumour cells from myeloma patients were analysed. RELN expression was moderate in CD19(+) B cells and was upregulated in CD138(+) plasma cells. A further upregulated RELN transcription was found in multiple myeloma cells. High expressions of RELN in myeloma cell lines as well as in patients were associated with hypomethylation in RELN promoter region. Demethylation increased RELN transcription in vitro. Together, we established that the methylation status of the promoter proximal cytosine-phospho-guanine dinucleotides determines the expression of RELN in myeloma cells. Copyright (C) 2016 John Wiley & Sons, Ltd.