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表观遗传机制与结直肠癌的致癌特性有关。

Epigenetic Mechanisms Are Involved in the Oncogenic Properties of in Colorectal Cancer.

作者信息

Gimeno-Valiente Francisco, Riffo-Campos Ángela L, Torres Luis, Tarazona Noelia, Gambardella Valentina, Cervantes Andrés, López-Rodas Gerardo, Franco Luis, Castillo Josefa

机构信息

Institute of Health Research, INCLIVA, 46010 Valencia, Spain.

Centro De Excelencia de Modelación y Computación Científica, Universidad de La Frontera, Temuco 01145, Chile.

出版信息

Cancers (Basel). 2021 Mar 21;13(6):1433. doi: 10.3390/cancers13061433.

DOI:10.3390/cancers13061433
PMID:33801071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8004037/
Abstract

The gene, which is up-regulated in colorectal cancer, plays a role in cell dissemination and metastasis. It encodes a zinc-finger protein, which interacts with histone methyltransferases G9A and EZH2. The expression of the two major mRNA isoforms 1 (coding for the full protein) and 2 was quantified by RT-qPCR in a cohort of 66 patients. The effects of silencing on the transcriptome of DLD1 and HCT116 cells were analysed by Clariom-S assays and validated by RT-qPCR. The recruitment of methyltransferases and the presence of H3K27me3 were studied by chromatin immunoprecipitation (ChIP). The ratio (isoform 2)/(isoform 1) negatively correlated with the relapsing of disease. The study of the transcriptome of DLD1 and HCT116 cells revealed that many genes affected by silencing are related to cancer. After crossing these results with the list of genes affected by silencing the histone methyltransferases (retrieved in silico), five genes were selected. ChIP analysis revealed that the recruitment of EZH2 is -dependent in , and ; the level of H3K27me3 changes in accordance. G9A also binds and in a -dependent manner. The results highlight the importance of epigenetics in cancer and open a novel therapeutic possibility, as inhibition of histone methyltransferases may reverse the disease-linked histone marks.

摘要

该基因在结直肠癌中上调，在细胞播散和转移中发挥作用。它编码一种锌指蛋白，该蛋白与组蛋白甲基转移酶G9A和EZH2相互作用。通过RT-qPCR对66例患者队列中两种主要mRNA亚型1（编码全长蛋白）和2的表达进行了定量。通过Clariom-S分析检测了沉默对DLD1和HCT116细胞转录组的影响，并通过RT-qPCR进行了验证。通过染色质免疫沉淀（ChIP）研究了甲基转移酶的募集和H3K27me3的存在情况。（亚型2）/（亚型1）的比率与疾病复发呈负相关。对DLD1和HCT116细胞转录组的研究表明，许多受沉默影响的基因与癌症相关。将这些结果与受组蛋白甲基转移酶沉默影响的基因列表（通过计算机检索）进行交叉比对后，选择了五个基因。ChIP分析表明，EZH2的募集在……中是……依赖性的，并且H3K27me3的水平也相应改变。G9A也以……依赖性方式结合……和……。这些结果突出了表观遗传学在癌症中的重要性，并开辟了一种新的治疗可能性，因为抑制组蛋白甲基转移酶可能会逆转与疾病相关的组蛋白标记。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/30ee7249807e/cancers-13-01433-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/3a511d785523/cancers-13-01433-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/bd65f6f074df/cancers-13-01433-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/4ae34d45ef12/cancers-13-01433-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/8907c9990411/cancers-13-01433-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/294d14accdc6/cancers-13-01433-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/1c347086e3ca/cancers-13-01433-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/30ee7249807e/cancers-13-01433-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/3a511d785523/cancers-13-01433-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/bd65f6f074df/cancers-13-01433-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/4ae34d45ef12/cancers-13-01433-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/8907c9990411/cancers-13-01433-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/294d14accdc6/cancers-13-01433-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/1c347086e3ca/cancers-13-01433-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/8004037/30ee7249807e/cancers-13-01433-g007.jpg

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