HDAC is indispensable for IFN-γ-induced B7-H1 expression in gastric cancer

HDAC is indispensable for IFN-γ-induced B7-H1 expression in gastric cancer
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HDAC 对于 IFN-γ 诱导的胃癌中 B7-H1 表达是不可或缺的

DOI:
10.1186/s13148-018-0589-6
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发表时间:
2018-12-11
影响因子:
5.7
通讯作者:
Tao, Kaixiong
Tao, Kaixiong
中科院分区:
医学1区
文献类型:
--
作者:
Deng, Rui;Zhang, Peng;Tao, Kaixiong

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背景B7同源物1(B7-H1)在肿瘤细胞上的过度表达是胃癌(GC)免疫逃避的重要机制。迫切需要阐明 B7-H1 表达的调控来指导 B7-H1 靶向癌症治疗。干扰素 γ (IFN-) 被认为是 B7-H1 表达背后的主要驱动力,最近,包括组蛋白乙酰化在内的表观遗传因素与该过程相关。在这里,我们研究了组蛋白脱乙酰酶 (HDAC) 在 GC 中 IFN 诱导的 B7-H1 表达中的潜在作用。还评估了 HDAC 小分子抑制剂 Vorinostat (SAHA) 对小鼠 GC 模型中肿瘤生长和 B7-H1 表达的影响。结果来自癌症基因组图谱的 RNA-seq 数据显示,与正常胃相比,GC 中 B7-H1、HDAC1-3、6-8 和 10 以及 SIRT1、3、5 和 6 的表达较高,而 HDAC5 和 SIRT4 的表达较低纸巾; GC 中 HDAC3 和 HDAC1 表达水平与 B7-H1 显着相关,各自的 r 值为 0.42(p
BackgroundB7 homolog 1 (B7-H1) overexpression on tumor cells is an important mechanism of immune evasion in gastric cancer (GC). Elucidation of the regulation of B7-H1 expression is urgently required to guide B7-H1-targeted cancer therapy. Interferon gamma (IFN-) is thought to be the main driving force behind B7-H1 expression, and epigenetic factors including histone acetylation are recently linked to the process. Here, we investigated the potential role of histone deacetylase (HDAC) in IFN--induced B7-H1 expression in GC. The effect of Vorinostat (SAHA), a small molecular inhibitor of HDAC, on tumor growth and B7-H1 expression in a mouse GC model was also evaluated.ResultsRNA-seq data from The Cancer Genome Atlas revealed that expression of B7-H1, HDAC1-3, 6-8, and 10 and SIRT1, 3, 5, and 6 was higher, and expression of HDAC5 and SIRT4 was lower in GC compared to that in normal gastric tissues; that HDAC3 and HDAC1 expression level significantly correlated with B7-H1 in GC with a respective r value of 0.42 (p