Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone.
Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone.
复制标题
DOI：
10.1186/1471-2407-14-495
复制
发表时间：
2014-07-09
期刊：
影响因子：
3.8
通讯作者：
Fellenberg J
中科院分区：
文献类型：
--
作者：
Lehner B;Kunz P;Saehr H;Fellenberg J
越来越多的证据表明，骨巨细胞瘤(GCT)中的肿瘤间质细胞群(GCTSC)来源于间充质干细胞(MSC)。在之前的一项研究中，我们发现了区分这些细胞类型的microRNA特征。5个差异表达的microRNAs位于14号染色体上的Dlk1-dio3区域。该区域的异常调控被认为影响细胞的生长、分化和癌症的发展。这项研究的目的是阐明Dlk1-dio3区域的失控在GCT发病机制中的作用。对GCTSCs和MSCs进行定量的基因和microRNA表达分析，并进行表观遗传修饰剂处理或不处理。亚硫酸氢盐测序法对差异甲基化区域进行甲基化分析。除了microRNA沉默外，我们还检测到与MSCs相比，GCTSCs中Dlk1、Meg3和Meg8的表达显著下调。对Meg3-DMR和IG-DMR的DNA甲基化分析显示，GCTS中IG-DMR存在频繁的超甲基化。表观遗传修饰可以恢复一些但不是所有已分析基因和microRNAs的表达，这表明了进一步的调控机制。Dlk1-dio3区基因和microRNAs的表观遗传沉默在GCTSCs中是一种常见的事件，部分是由IG-DMR中的高甲基化介导的。已鉴定的基因、microRNAs和microRNA靶基因可能成为改进GCT诊断和治疗策略的有价值的靶点。
Growing evidence exists that the neoplastic stromal cell population (GCTSC) within giant cell tumors (GCT) originates from mesenchymal stem cells (MSC). In a previous study we identified a microRNA signature that differentiates between these cell types. Five differentially expressed microRNAs are located within the Dlk1-Dio3 region on chromosome 14. Aberrant regulation within this region is known to influence cell growth, differentiation and the development of cancer. The aim of this study was to elucidate the involvement of deregulations within the Dlk1-Dio3 region in GCT pathogenesis. Quantitative gene and microRNA expression analyses were performed on GCTSCs and MSCs with or without treatment with epigenetic modifiers. Methylation analysis of differentially methylated regions was performed by bisulfite sequencing. In addition to microRNA silencing we detected a significant downregulation of Dlk1, Meg3 and Meg8 in GCTSCs compared to MSCs. DNA methylation analyses of the Meg3-DMR and IG-DMR revealed a frequent hypermethylation within the IG-DMR in GCTs. Epigenetic modification could restore expression of some but not all analyzed genes and microRNAs suggesting further regulatory mechanisms. Epigenetic silencing of genes and microRNAs within the Dlk1-Dio3 region is a common event in GCTSCs, in part mediated by hypermethylation within the IG-DMR. The identified genes, micro RNAs and microRNA target genes might be valuable targets for the development of improved strategies for GCT diagnosis and therapy.
登录
查看更多内容
影响因子：
8
作者：
Abujiang, P;Mori, TJ;Hiai, H
通讯作者：
Hiai, H
DOI：
10.3816/clm.2008.n.021
发表时间：
2008-06-01
期刊：
CLINICAL LYMPHOMA & MYELOMA
影响因子：
--
作者：
Benetatos, Leonidas;Dasoula, Aggeliki;Bourantas, Konstantinos L.
通讯作者：
Bourantas, Konstantinos L.
影响因子：
--
作者：
Bando, T;Kato, Y;Isobe, M
通讯作者：
Isobe, M
影响因子：
3.3
作者：
Wülling, M;Delling, G;Kaiser, E
通讯作者：
Kaiser, E
影响因子：
64.8
作者：
通讯作者：
--