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锌指蛋白ZC3H18在食管癌组织中异常表达,并促进食管癌细胞的增殖。

Zinc finger protein ZC3H18 is abnormally expressed in esophageal cancer tissues and facilitates the proliferation of esophageal cancer cells.

作者信息

Zhang Yujin, Wan Yilong, Li Jiaxi, Ju Sheng, Tong Xin, Wu Ji, Wu Hao, Zhang Liuqing, Shao Shengxiang, Wang Yuhong, Guo Lingchuan, Zhao Jun, Cao Lei, Jiang Dong

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

出版信息

Front Immunol. 2025 Feb 25;16:1556509. doi: 10.3389/fimmu.2025.1556509. eCollection 2025.

Abstract

INTRODUCTION

Esophageal cancer presents significant challenges due to the limited efficacy and severe side effects associated with conventional treatments. The identification of epigenetic regulatory molecules that are aberrantly expressed in tumors is crucial for elucidating the mechanisms underlying the development and progression of esophageal cancer.

METHODS

We performed high-throughput methylation level analysis on cancerous and adjacent tissues from 25 patients, identifying the differentially methylated gene utilizing Bismark software and data from TCGA. Esophageal cancer cell lines with ZC3H18 knockdown were used to validate the biological role of ZC3H18 in tumorigenesis and . Eukaryotic transcriptome sequencing analysis was conducted to investigate the potential mechanisms underlying ZC3H18 function.

RESULTS

We identified 30 genes exhibiting significant methylation differences between cancerous and adjacent non-cancerous tissues in 25 patients. Subsequent analysis utilizing the TCGA database revealed that the gene is aberrantly expressed in tumor tissues and is closely associated with patient prognosis. Examination of esophageal cancer tissue samples demonstrated overexpression of the ZC3H18 protein, which was positively correlated with adverse prognosis indicators, including tumor differentiation, stage, and invasion depth. ZC3H18 knockdown significantly inhibited cellular proliferation, migration, invasion, and damage repair. Additionally, ZC3H18 significantly promoted tumor growth . The expression of various cytokeratins was significantly reduced following the gene knockdown. ZC3H18 and multiple keratins were co-localized in esophageal cancer tissue.

DISCUSSION

gene exhibits differential methylation in esophageal cancer was positively correlated with unfavorable patient prognosis. ZC3H18 plays a critical role in the regulation of biological functions within esophageal tumors.

摘要

引言

由于传统治疗方法疗效有限且副作用严重,食管癌带来了重大挑战。鉴定在肿瘤中异常表达的表观遗传调控分子对于阐明食管癌发生和发展的潜在机制至关重要。

方法

我们对25例患者的癌组织和癌旁组织进行了高通量甲基化水平分析,利用Bismark软件和来自TCGA的数据鉴定差异甲基化基因。使用敲低ZC3H18的食管癌细胞系来验证ZC3H18在肿瘤发生中的生物学作用。进行真核转录组测序分析以研究ZC3H18功能的潜在机制。

结果

我们在25例患者的癌组织和癌旁非癌组织中鉴定出30个表现出显著甲基化差异的基因。随后利用TCGA数据库进行的分析显示,该基因在肿瘤组织中异常表达,且与患者预后密切相关。对食管癌组织样本的检测显示ZC3H18蛋白过表达,其与不良预后指标呈正相关,包括肿瘤分化、分期和浸润深度。敲低ZC3H18显著抑制细胞增殖、迁移、侵袭和损伤修复。此外,ZC3H18显著促进肿瘤生长。敲低该基因后,各种细胞角蛋白的表达显著降低。ZC3H18与多种角蛋白在食管癌组织中共定位。

讨论

在食管癌中表现出差异甲基化的基因与患者不良预后呈正相关。ZC3H18在食管肿瘤生物学功能的调节中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/11894379/b83bcfb3e83c/fimmu-16-1556509-g001.jpg

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