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骨肉瘤中组蛋白H4赖氨酸20三甲基化的缺失与组蛋白甲基转移酶SUV420H2的异常表达有关。

Loss of histone H4 lysine 20 trimethylation in osteosarcoma is associated with aberrant expression ofhistone methyltransferase SUV420H2.

作者信息

Piao Lianhua, Yuan Xiaofeng, Wang Luhui, Xu Xiaoshuang, Zhuang Ming, Li Jinggao, Kong Ren, Liu Zhiwei

机构信息

Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou, Jiangsu 213001, P.R. China.

Department of Orthopaedics, The Third Affiliated Hospital of SooChow University, Changzhou, Jiangsu 213000, P.R. China.

出版信息

Oncol Lett. 2020 Oct;20(4):26. doi: 10.3892/ol.2020.11887. Epub 2020 Jul 16.

DOI:10.3892/ol.2020.11887
PMID:32774499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7406877/
Abstract

Epigenetic modifications of histones have crucial roles in various types of cancers. The aberrant trimethylation of histone H4 at lysine 20 (H4K20) has been implicated in carcinogenesis. At present, the status of trimethylation at H4k20 (H4K20me3) in osteosarcoma (OS), the predominant bone cancer in humans, is unknown. In the present study, a genome-wide decrease was observed in H4K20me3 levels in OS tissues and cell lines. Reduced levels of lysine methyltransferase 5C (SUV420H2), the histone methyltranferase responsible for modification of H4K20me3, was also observed in OS cells with the associated loss of H4K20me3. Furthermore, a total of 507 SUV420H2-regulated genes were identified through RNA-seq and a number of candidate genes were further validated. Bioinformatic analysis revealed an association between SUV420H2 and multiple signaling pathway, including the mitogen-activated protein kinase, P53, transforming growth factor and the ErbB pathways. These results demonstrated that there are aberrant levels of H4K20me3 and SUV420H2 in OS, and highlighted H4K20me3 as a candidate biomarker for the early detection of OS.

摘要

组蛋白的表观遗传修饰在各类癌症中起着关键作用。组蛋白H4赖氨酸20位点(H4K20)的异常三甲基化与癌症发生有关。目前,在人类主要的骨癌骨肉瘤(OS)中,H4K20位点的三甲基化状态(H4K20me3)尚不清楚。在本研究中,观察到骨肉瘤组织和细胞系中H4K20me3水平在全基因组范围内降低。在骨肉瘤细胞中也观察到负责H4K20me3修饰的组蛋白甲基转移酶赖氨酸甲基转移酶5C(SUV420H2)水平降低,同时伴有H4K20me3的缺失。此外,通过RNA测序共鉴定出507个受SUV420H2调控的基因,并对一些候选基因进行了进一步验证。生物信息学分析揭示了SUV420H2与多种信号通路之间的关联,包括丝裂原活化蛋白激酶、P53、转化生长因子和表皮生长因子受体(ErbB)信号通路。这些结果表明,骨肉瘤中存在异常水平的H4K20me3和SUV420H2,并突出了H4K20me3作为骨肉瘤早期检测候选生物标志物的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/2dfd4d8fe84a/ol-20-04-11887-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/c9add7eeebbf/ol-20-04-11887-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/d5b553477116/ol-20-04-11887-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/f6178c9117ea/ol-20-04-11887-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/5b77164d70fe/ol-20-04-11887-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/50a8c7297406/ol-20-04-11887-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/2dfd4d8fe84a/ol-20-04-11887-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/c9add7eeebbf/ol-20-04-11887-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/d5b553477116/ol-20-04-11887-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/f6178c9117ea/ol-20-04-11887-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/5b77164d70fe/ol-20-04-11887-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/50a8c7297406/ol-20-04-11887-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf1/7406877/2dfd4d8fe84a/ol-20-04-11887-g05.jpg

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