Aberrant DNA Methylation Patterns of Deleted in Liver Cancer 1 Isoforms in Hepatocellular Carcinoma.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Junhai Pan, Duguang Li, Xiaoxiao Fan, Jiaxi Cheng, Shengxi Jin, Peng Chen, Hui Lin, Yirun Li
{"title":"Aberrant DNA Methylation Patterns of Deleted in Liver Cancer 1 Isoforms in Hepatocellular Carcinoma.","authors":"Junhai Pan,&nbsp;Duguang Li,&nbsp;Xiaoxiao Fan,&nbsp;Jiaxi Cheng,&nbsp;Shengxi Jin,&nbsp;Peng Chen,&nbsp;Hui Lin,&nbsp;Yirun Li","doi":"10.1089/dna.2022.0384","DOIUrl":null,"url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), a common primary liver cancer, is the third leading cause of death worldwide. DNA methylation changes are common in HCC and have been studied to be associated with hepatocarcinogenesis. In our study, we used the MassARRAY<sup>®</sup> EpiTYPER technology to investigate the methylation differences of deleted in liver cancer 1 (<i>DLC1</i>) (isoform 1 and 3) promoter between HCC tissues and corresponding adjacent noncancerous tissues and the association between methylation levels and clinicopathological features. In addition, the modified CRISPR-Cas9 system and the DNA methyltransferase inhibitor (DNMTi) were utilized to explore the functional correlation of epigenetic modifications and <i>DLC1</i> gene regulation. The methylation levels of the <i>DLC1</i> isoforms in HCC samples were found significantly lower than those in the adjacent noncancerous tissues (all <i>p</i> < 0.0001). Also, we found that the expression of <i>DLC1</i> could be bidirectionally regulated by the modified CRISPR-Cas9 system and the DNMTi. Moreover, the hypomethylation of <i>DLC1</i> in HCC samples was connected with the presence of satellite lesions (<i>p</i> = 0.0305) and incomplete tumor capsule (<i>p</i> = 0.0204). Receiver operator characteristic curve analysis demonstrated that the methylation levels of <i>DLC1</i> could be applied to discriminate HCC patients (area under the curve = 0.728, <i>p</i> < 0.0001). The hypomethylation status was a key regulatory mechanism of <i>DLC1</i> expression and might serve as a potential biomarker for HCC.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 3","pages":"140-150"},"PeriodicalIF":2.6000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA and cell biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/dna.2022.0384","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 1

Abstract

Hepatocellular carcinoma (HCC), a common primary liver cancer, is the third leading cause of death worldwide. DNA methylation changes are common in HCC and have been studied to be associated with hepatocarcinogenesis. In our study, we used the MassARRAY® EpiTYPER technology to investigate the methylation differences of deleted in liver cancer 1 (DLC1) (isoform 1 and 3) promoter between HCC tissues and corresponding adjacent noncancerous tissues and the association between methylation levels and clinicopathological features. In addition, the modified CRISPR-Cas9 system and the DNA methyltransferase inhibitor (DNMTi) were utilized to explore the functional correlation of epigenetic modifications and DLC1 gene regulation. The methylation levels of the DLC1 isoforms in HCC samples were found significantly lower than those in the adjacent noncancerous tissues (all p < 0.0001). Also, we found that the expression of DLC1 could be bidirectionally regulated by the modified CRISPR-Cas9 system and the DNMTi. Moreover, the hypomethylation of DLC1 in HCC samples was connected with the presence of satellite lesions (p = 0.0305) and incomplete tumor capsule (p = 0.0204). Receiver operator characteristic curve analysis demonstrated that the methylation levels of DLC1 could be applied to discriminate HCC patients (area under the curve = 0.728, p < 0.0001). The hypomethylation status was a key regulatory mechanism of DLC1 expression and might serve as a potential biomarker for HCC.

肝癌1亚型中缺失的异常DNA甲基化模式
肝细胞癌(HCC)是一种常见的原发性肝癌,是全球第三大死亡原因。DNA甲基化变化在HCC中很常见,并已被研究与肝癌发生有关。在我们的研究中,我们使用MassARRAY®EpiTYPER技术研究了肝癌组织和相应的邻近非癌组织中缺失的肝癌1 (DLC1)(异构体1和3)启动子的甲基化差异以及甲基化水平与临床病理特征之间的关系。此外,利用修饰后的CRISPR-Cas9系统和DNA甲基转移酶抑制剂(DNMTi),探索表观遗传修饰与DLC1基因调控的功能相关性。发现HCC样本中dcl1亚型的甲基化水平显著低于邻近非癌组织(所有p dcl1都可以被修饰的CRISPR-Cas9系统和DNMTi双向调节)。此外,HCC样本中DLC1的低甲基化与卫星病变(p = 0.0305)和肿瘤包膜不完整(p = 0.0204)的存在有关。受体操作者特征曲线分析表明,DLC1的甲基化水平可用于鉴别HCC患者(曲线下面积= 0.728,p DLC1表达),并可能作为HCC的潜在生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
DNA and cell biology
DNA and cell biology 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
93
审稿时长
1.5 months
期刊介绍: DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信