服务电话:0571-86871128赛澜生物技术(杭州)有限公司欢迎您!
您所在的位置:首页 » 新闻动态 » 科研动态

服务承诺

严格的知识产权保护体系
经验丰富的服务团队和管理团队
周全的实验设计及严格的操作流程
完善的质量管理体系

JCI:美研究员揭示KLF6在脂肪肉瘤的表观遗传影响

浏览:1495 | 日期:2015-08-12 | 作者: admin

2015年8月4日发表的《The JouRNAl of Clinical Investigation》中德克萨斯大学MD安德森癌症中心Lynda Chin的一篇研究论文,研究指出在脂肪肉瘤中抑制KLF6的表达会提高H3K9me3的水平,从而促进其去分化表型的发生。Emily Z. Keung等人发文,证实了KLF6在脂肪肉瘤的表观遗传学上起到重要作用。

KLF6(Kruppel-like factor 6)是一个普遍表达的核转录调控因子、抑癌基因,它的失活或表达异常参与了多种肿瘤的发生发展。脂肪肉瘤(LPS)可分为4种不同的亚型,其中最常见的为高分化LPS(WDLPS)和去分化LPS(DDLPS)。WDLPS是典型的低级水平,而DDLPS是高级的、具有侵略性并伴随更坏的预后。WDLPS和DDLPS经常共同出现在病患中,然而,DDLPS是否独立地来源于WDLPS,还是表观遗传改变这些亚型的基本病理学差异?这些问题仍然是未知的。

在本文中,研究者们通过研究从151个病患肿瘤样本,描述了9个表观遗传标记,并揭露了在DDLPS肿瘤中组蛋白H3赖氨酸9(H3K9me3)的高甲基化水平。对来自病患的细胞系进行综合ChIP-seq和基因表达分析,结果显示H3K9me3介导涉及分化和迁移的基因的微分调节。其中KLF6在DDLP中的水平降低了,而同时H3K9me3在相关领域的表达提高了。用毛壳素对H3K9me3进行药物抑制,减少了DDLPS的增殖并增强了与脂肪形成相关的因子——PPARγ, CEBPα, and CEBPβ的表达,这意味着增加H3K9me3可能介导DDLPS相关的侵略性和去分化特性。在DDLPS细胞中过表达KLF6部分地模拟毛壳素药物治疗并诱导表型变化,与脂肪细胞分化现象一致,表明增加H3K9me3有可能是通过KLF6来影响细胞的。综上所述,研究者们对WDLPS和DDLPS之间的转换提供了表观遗传学上的证据。
JCI:美研究员揭示KLF6在脂肪肉瘤的表观遗传影响

原文链接:

increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma

原文摘要:

Liposarcoma (LPS) can be divided into 4 different subtypes, of which well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) are the most common. WDLPS is typically low grade, whereas DDLPS is high grade, aggressive, and carries a worse prognosis. WDLPS and DDLPS frequently co-occur in patients. However, it is not clear whether DDLPS arises independently from WDLPS, or whether epigenomic alterations underly the histopathological differences of these subtypes. Here, we profiled 9 epigenetic marks in tumor samples from 151 patients with LPS and showed elevated trimethylation of histone H3 at Lys9 (H3K9me3) levels in DDLPS tumors. Integrated ChIP-seq and gene expression analyses of patient-derived cell lines revealed that H3K9me3 mediates differential regulation of genes involved in cellular differentiation and migration. Among these, Kruppel-like factor 6 (KLF6) was reduced in DDLPS, with increased H3K9me3 at associated regulatory regions. Pharmacologic inhibition of H3K9me3 with chaetocin decreased DDLPS proliferation and increased expression of the adipogenesis-associated factors PPARγ, CEBPα, and CEBPβ, suggesting that increased H3K9me3 may mediate DDLPS-associated aggressiveness and dedifferentiation properties. KLF6 overexpression partially phenocopied chaetocin treatment in DDLPS cells and induced phenotypic changes that were consistent with adipocytic differentiation, suggesting that the effects of increased H3K9me3 may be mediated through KLF6. In conclusion, we provide evidence of an epigenetic basis for the transition between WDLPS and DDLPS.

doi:10.1172/JCI77976.

 

  • 点击这里给我发消息
  • 点击这里给我发消息
  • 点击这里给我发消息
友情链接
Copyright © 2003-2015 68design.net, All Rights Reserved地址:杭州市滨江区滨安路688号天和高科技产业园G幢5层 赛澜生物技术(杭州)有限公司