ZC3H18 regulates alternative splicing and related genes in cervical cancer.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-09-09 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1621238

Wenjuan Chen, Chenying Liu, Siyi Li, Xingyun Xie, Dan Hu, Yaobin Lin

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引用次数: 0

Abstract

Introduction: Alternative splicing (AS) and RNA-binding proteins (RBPs) have been implicated in various diseases. However, a comprehensive understanding of their role in RNA metabolism, progression, and metastasis in cervical cancer remains elusive. This study aimed to identify the potential effect of zinc finger CCCH-type containing 18 (ZC3H18) in cervical cancer.

Methods: The Gene Expression Omnibus (GEO) dataset (GSE94427) was used to analyze the expression level of ZC3H18 in HeLa cells and its regulated alternative splicing events (ASEs). The Cancer Genome Atlas (TCGA) cervical cancer dataset and in vitro experiments were used for verification. The signaling pathways and functions of ZC3H18-regulated ASEs were investigated through enrichment analysis.

Results: Knockdown of ZC3H18 in HeLa cells increased the expression of 106 genes but decreased the expression of 226 genes. ZC3H18 was found to be involved in the regulation of 1,830 ASEs. The AS genes were enriched in cervical cancer-related signaling pathways. Validation using 39 cervical cancer samples from the TCGA database showed that 20 cases had low ZC3H18 expression and 19 had high expression. By integrating GEO and TCGA datasets along with in vitro experiments, 18 ASEs with consistent changes were identified.

Discussion: This study demonstrated that ZC3H18 extensively regulates AS of cancer-associated pathways in HeLa cells and cervical cancer tissues. The identification of ZC3H18-regulated ASEs may provide potential targets for cervical cancer treatment.

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ZC3H18调控子宫颈癌的选择性剪接及相关基因。

选择性剪接（AS）和rna结合蛋白（rbp）与多种疾病有关。然而，对它们在子宫颈癌的RNA代谢、进展和转移中的作用的全面理解仍然是难以捉摸的。本研究旨在探讨含18 （ZC3H18）锌指ccch型在宫颈癌中的潜在作用。方法：利用GEO数据集（GSE94427）分析ZC3H18在HeLa细胞中的表达水平及其调控的选择性剪接事件（ASEs）。使用癌症基因组图谱（TCGA）宫颈癌数据集和体外实验进行验证。通过富集分析研究zc3h18调控的酶的信号通路和功能。结果：敲低ZC3H18可使HeLa细胞中106个基因表达增加，226个基因表达减少。ZC3H18被发现参与了1,830个ase的调控。AS基因在宫颈癌相关信号通路中富集。通过TCGA数据库中的39例宫颈癌样本验证，ZC3H18低表达20例，高表达19例。通过整合GEO和TCGA数据集以及体外实验，鉴定出18个具有一致变化的ase。讨论：本研究表明ZC3H18广泛调控HeLa细胞和宫颈癌组织中AS的癌相关通路。zc3h18调控的ase的鉴定可能为宫颈癌治疗提供潜在靶点。

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

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.