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CPSF4-mediated regulation of alternative splicing of HMG20B facilitates the progression of triple-negative breast cancer

  • 0Department of Breast Surgery, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Journal of Translational Medicine +

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December 28, 2024

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December 28, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Cleavage and polyadenylation specificity factor 4 (CPSF4) promotes triple-negative breast cancer (TNBC) progression by regulating alternative splicing of HMG20B. This study identifies CPSF4 as a potential prognostic and therapeutic biomarker for TNBC.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Aberrant alternative splicing (AS) is implicated in tumor progression.
  • Cleavage and polyadenylation specificity factor 4 (CPSF4) is a key regulator of AS.
  • The role of CPSF4 in triple-negative breast cancer (TNBC) progression via AS remains largely unknown.

Purpose Of The Study

  • To investigate the prognostic value of CPSF4 in TNBC.
  • To identify critical AS events regulated by CPSF4 in TNBC.

Main Methods

  • Analysis of CPSF4 expression and prognostic significance in TNBC patient data.
  • RNA immunoprecipitation sequencing (RIP-seq) and RNA sequencing (RNA-seq) to identify CPSF4 targets and global transcriptome changes.
  • Validation of CPSF4-regulated alternative splicing events (ASEs) and functional assays in TNBC cells.

Main Results

  • Elevated CPSF4 expression in TNBC correlates with poor prognosis.
  • CPSF4 overexpression enhances TNBC cell proliferation and migration; knockdown inhibits these processes.
  • CPSF4 regulates numerous genes involved in cancer-related pathways, including mRNA processing and cell cycle.
  • CPSF4 specifically inhibits alternative 3' splice site events of HMG20B, promoting TNBC cell proliferation, migration, and invasion.

Conclusions

  • CPSF4 drives TNBC progression through AS regulation of HMG20B.
  • CPSF4 represents a promising prognostic, diagnostic, and therapeutic target for TNBC.

Keywords:

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