Whole-Genome Methylation Sequencing Analysis and Functional Verification of LIM-Homeobox Family Genes in Cervical Cancer.

IF 2.1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
International Journal of General Medicine Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI:10.2147/IJGM.S451841
Rong Yu, Qin Yu, Jie Shi, Xue Meng, Zhiyuan Deng, Jing Suo, Hao Yang
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引用次数: 0

Abstract

Background: Gene methylation in cells is an important factor in tumorigenesis, and radiotherapy can change DNA methylation in cells. In this study, complete genome methylation sequencing (BS-Seq) technology was used to analyze the genome-wide methylation of patients with cervical cancer before and after radiotherapy.

Methods: Three pairs of cervical squamous cell carcinoma samples were collected from patients before and after radiotherapy in July 2020. Genome-wide DNA methylation profiles were generated using WGBS. Bioinformatics analysis was conducted to identify differential methylation regions (DMRs) and their associated genes and pathways. The study focused on the methylation changes of LHX2, LHX5, and LHX9 genes, assessing their expression levels using qRT-PCR and correlating these changes with cervical cancer stages.

Results: MCG was the main way of genomic DNA methylation in the three patients. The DNA methylation level and methylation density on each chromosome varied greatly. As revealed by comparison of methylation before and after radiation in the three patients, 1287, 1261 and 789 differential methylation genes were identified, respectively. 3) Combined with clinical treatment, methylation level difference and correlation enrichment analysis, it was found that LHX2, LHX5 and LHX9 were closely related to the occurrence and development of cervical cancer. After 5-Aza-DC and radiotherapy, the methylation of the CpG islands in LHX2, LHX5 and LHX9 genes in these patients was decreased (p < 0.01), and the mRNA and protein expression levels were relatively increased (p < 0.01).

Conclusion: In our present work, genome-wide DNA methylation maps of cervical cancer tissues before and after radiotherapy were successfully constructed. We found that LHX5 and LHX9 genes are closely related to cervical cancer. LHX5 and LHX9 have a negative effect on cervical cancer. The migration ability of LHX9 silenced cells was significantly enhanced after irradiation.

宫颈癌中 LIM-Homeobox 家族基因的全基因组甲基化测序分析与功能验证
背景:细胞内基因甲基化是肿瘤发生的重要因素,而放疗可改变细胞内DNA甲基化。本研究采用全基因组甲基化测序(BS-Seq)技术对宫颈癌患者放疗前后的全基因组甲基化进行分析。方法:收集2020年7月放疗前后患者宫颈鳞状细胞癌标本3对。使用WGBS生成全基因组DNA甲基化谱。生物信息学分析鉴定差异甲基化区(DMRs)及其相关基因和途径。本研究重点关注LHX2、LHX5和LHX9基因的甲基化变化,利用qRT-PCR技术评估其表达水平,并将这些变化与宫颈癌分期进行相关性分析。结果:MCG是3例患者基因组DNA甲基化的主要途径。各染色体上的DNA甲基化水平和甲基化密度差异很大。对比3例患者放疗前后的甲基化,分别鉴定出1287、1261和789个差异甲基化基因。3)结合临床治疗、甲基化水平差异及相关富集分析,发现LHX2、LHX5、LHX9与宫颈癌的发生发展密切相关。5-Aza-DC及放疗后,患者LHX2、LHX5、LHX9基因CpG岛甲基化程度降低(p < 0.01), mRNA和蛋白表达水平相对升高(p < 0.01)。结论:本研究成功构建了宫颈癌放疗前后组织全基因组DNA甲基化图谱。我们发现LHX5和LHX9基因与宫颈癌密切相关。LHX5和LHX9对宫颈癌有负面作用。辐照后LHX9沉默细胞的迁移能力明显增强。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International Journal of General Medicine
International Journal of General Medicine Medicine-General Medicine
自引率
0.00%
发文量
1113
审稿时长
16 weeks
期刊介绍: The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal. As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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