Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression.
Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression.
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DOI：
10.1186/s12885-017-3256-y
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发表时间：
2017-04-12
期刊：
影响因子：
3.8
通讯作者：
Bernard-Gallon D
中科院分区：
文献类型：
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作者：
Ngollo M;Lebert A;Daures M;Judes G;Rifai K;Dubois L;Kemeny JL;Penault-Llorca F;Bignon YJ;Guy L;Bernard-Gallon D
H3 K27 me 3组蛋白标记形成基因转录的抑制。在前列腺癌中，H3 K27 me 3标记的失调可能在前列腺肿瘤进展中起作用。我们使用染色质免疫沉淀（ChIP）和2X 400 K启动子微阵列研究全基因组H3 K27 me 3组蛋白甲基化谱，以确定前列腺癌患者活检样本中的差异富集区域。在34个前列腺肿瘤中评估H3 K27 me 3标记：11个具有Gleason评分> 7（GS > 7），10个具有Gleason评分≤ 7（GS ≤ 7），和13个形态正常的前列腺样品。在此，H3 K27 me 3谱分析在健康对照组中鉴定了启动子区域上平均386个富集基因，而GS ≤ 7组中为545个基因，GS > 7组中为748个基因。然后，我们进行了因子判别分析（FDA），并使用ANOVA比较了前列腺肿瘤活检和正常活检中的富集基因，以确定显着差异富集基因。分析鉴定了ALG 5、EXOSC 8、CBX 1、GRID 2、GRIN 3B、ING 3、MYO 1D、NPHP 3-AS 1、MSH 6、FBXO 11、SND 1、SPATS 2、TENM 4和TRA 2A基因。这些基因可能与前列腺癌有关。值得注意的是，H3 K27 me 3组蛋白标志物在预后不良的前列腺癌中成为一种新的调节机制。我们的研究结果指出，表观遗传标记H3 K27 me 3作为一个重要的事件，在前列腺癌的发生和发展。本文报道的结果为前列腺癌的发病机制提供了新的分子见解。
H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression. We investigated genome-wide H3K27me3 histone methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K promoter microarrays to identify differentially-enriched regions in biopsy samples from prostate cancer patients. H3K27me3 marks were assessed in 34 prostate tumors: 11 with Gleason score > 7 (GS > 7), 10 with Gleason score ≤ 7 (GS ≤ 7), and 13 morphologically normal prostate samples. Here, H3K27me3 profiling identified an average of 386 enriched-genes on promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. We then ran a factorial discriminant analysis (FDA) and compared the enriched genes in prostate-tumor biopsies and normal biopsies using ANOVA to identify significantly differentially-enriched genes. The analysis identified ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes. These genes are possibly associated with prostate cancer. Notably, the H3K27me3 histone mark emerged as a novel regulatory mechanism in poor-prognosis prostate cancer. Our findings point to epigenetic mark H3K27me3 as an important event in prostate carcinogenesis and progression. The results reported here provide new molecular insights into the pathogenesis of prostate cancer.