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ZC3H18 regulates alternative splicing and related genes in cervical cancer

Wenjuan Chen1, Chenying Liu1, Siyi Li1

  • 1Department of Radiotherapy, Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.

Frontiers in Genetics
|September 25, 2025
PubMed
Abstract

Insights

Zinc finger CCCH-type containing 18 (ZC3H18) regulates alternative splicing (AS) in cervical cancer cells and tissues. Identifying ZC3H18-regulated AS events offers potential therapeutic targets for cervical cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • Alternative splicing (AS) and RNA-binding proteins (RBPs) are implicated in disease pathogenesis.
  • The specific roles of AS and RBPs in cervical cancer progression and metastasis are not fully understood.
  • Zinc finger CCCH-type containing 18 (ZC3H18) is a potential regulator of RNA metabolism.

Purpose of the Study:

  • To investigate the role of ZC3H18 in cervical cancer.
  • To identify ZC3H18-regulated alternative splicing events (ASEs) in cervical cancer.
  • To explore the potential of ZC3H18-regulated ASEs as therapeutic targets.

Main Methods:

  • Analysis of Gene Expression Omnibus (GEO) dataset (GSE94427) for ZC3H18 expression and regulated ASEs in HeLa cells.
  • Utilized The Cancer Genome Atlas (TCGA) cervical cancer dataset and in vitro experiments for validation.
  • Performed enrichment analysis to investigate signaling pathways and functions of ZC3H18-regulated ASEs.

Main Results:

  • ZC3H18 knockdown altered the expression of 332 genes (106 increased, 226 decreased) in HeLa cells.
  • ZC3H18 was found to regulate 1,830 alternative splicing events (ASEs).
  • Integration of GEO, TCGA, and in vitro data identified 18 consistently altered ASEs, enriched in cancer-associated pathways.

Conclusions:

  • ZC3H18 extensively regulates alternative splicing of cancer-associated pathways in cervical cancer.
  • ZC3H18 plays a significant role in cervical cancer RNA metabolism.
  • Identified ZC3H18-regulated ASEs represent potential therapeutic targets for cervical cancer.
Keywords:
RNA-binding proteinsZC3H18alternative splicing eventscervical cancergenes

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