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肺癌中串联取向介导的下游基因的表观遗传沉默。

Epigenetic silencing of downstream genes mediated by tandem orientation in lung cancer.

机构信息

Institute for Genetics; Justus-Liebig-University, 35392, Giessen, Germany.

Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.

出版信息

Sci Rep. 2017 Jun 20;7(1):3896. doi: 10.1038/s41598-017-04248-w.

DOI:10.1038/s41598-017-04248-w
PMID:28634396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5478622/
Abstract

Epigenetic deregulation is of importance in tumorigenesis. In particular CpG islands (CGI), are frequently hypermethylated. Here, genome-wide DNA-methylation profiles of 480,000 CpGs in lung cancer cells were generated. It was observed that intra- and intergenic CGI exhibited higher methylation compared to normal cells. The functional annotation of hypermethylated CGI revealed that the hypermethylation was associated with homeobox domain genes and targets marked by repressive histone modifications. The strongest methylation variation was observed in transitional areas of CGI, termed shores. 5'-shores of promoter-associated CGI in lung cancer cell lines were higher methylated than 3'-shores. Within two tandem-oriented genes, a significant hypermethylation of the downstream-located CGI promoters was revealed. Hypermethylation correlates with the length of the intergenic region between such tandem genes. As the RASSF1A tumor suppressor gene represents such a downstream tandem gene, its silencing was analyzed using an inducible system. It was determined that the induction of an upstream gene led to a repression of RASSF1A through a process involving histone deacetylases and CPSF1. A tumor-specific increase in expression of histone deacetylases and CPSF1 was detected in lung cancer. Our results suggest that the downstream gene could be susceptible to epigenetic silencing when organized in a tandem orientation.

摘要

表观遗传失调在肿瘤发生中具有重要意义。特别是 CpG 岛（CGI）经常发生过度甲基化。在这里，生成了肺癌细胞中 480,000 个 CpG 的全基因组 DNA 甲基化谱。观察到基因内和基因间 CGI 表现出比正常细胞更高的甲基化。对过度甲基化 CGI 的功能注释表明，过度甲基化与同源盒结构域基因和受抑制组蛋白修饰标记的靶基因有关。在 CGI 的过渡区域（称为shore）观察到最强的甲基化变化。在肺癌细胞系中，与启动子相关的 CGI 的 5'-shore 比 3'-shore 甲基化程度更高。在两个串联定向基因中，下游定位的 CGI 启动子的显著过度甲基化被揭示。过度甲基化与这种串联基因之间的基因间区域的长度相关。由于 RASSF1A 肿瘤抑制基因代表这样的下游串联基因，因此使用诱导系统分析了其沉默。确定诱导上游基因会通过涉及组蛋白去乙酰化酶和 CPSF1 的过程导致 RASSF1A 的抑制。在肺癌中检测到组蛋白去乙酰化酶和 CPSF1 的肿瘤特异性表达增加。我们的研究结果表明，当以串联取向组织时，下游基因可能容易受到表观遗传沉默的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/00f72f50fcca/41598_2017_4248_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/e46737cb2175/41598_2017_4248_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/c72fefc03f33/41598_2017_4248_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/5a84fe589a08/41598_2017_4248_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/63e4a41624c4/41598_2017_4248_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/21bfb7048037/41598_2017_4248_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/00f72f50fcca/41598_2017_4248_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/e46737cb2175/41598_2017_4248_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/c72fefc03f33/41598_2017_4248_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/5a84fe589a08/41598_2017_4248_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/63e4a41624c4/41598_2017_4248_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/21bfb7048037/41598_2017_4248_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3455/5478622/00f72f50fcca/41598_2017_4248_Fig6_HTML.jpg

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Oncol Rep. 2016 Jul;36(1):589-97. doi: 10.3892/or.2016.4811. Epub 2016 May 16.
3
Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential.肿瘤抑制基因的表观遗传沉默：范例、谜题与潜力。
Genome Biol. 2023 Jul 10;24(1):161. doi: 10.1186/s13059-023-03000-0.
4
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Am J Cancer Res. 2022 Oct 15;12(10):4566-4583. eCollection 2022.
5
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6
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