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Updated: May 9, 2025

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IGF2BP3 recruits NUDT21 to regulate SPTBN1 alternative polyadenylation and drive ovarian cancer progression

Xin Luo1, Lingcui Xie1, Xiaohui Ma1

  • 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Communications Biology
|April 29, 2025
PubMed

Insights

This study reveals NUDT21 promotes ovarian cancer by altering SPTBN1 gene expression via m6A modification. Targeting this pathway offers new therapeutic strategies for ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian cancer (OC) is a leading cause of gynecological cancer deaths.
  • Alternative polyadenylation (APA) is a key post-transcriptional regulator implicated in tumor progression.

Purpose of the Study:

  • To investigate the role of APA regulator NUDT21 in ovarian cancer.
  • To elucidate the regulatory mechanism of SPTBN1 alternative polyadenylation in OC progression.

Main Methods:

  • Identified NUDT21 upregulation in OC tissues.
  • Investigated the interaction between IGF2BP3 and NUDT21.
  • Analyzed SPTBN1 transcript variants and their functions.

Main Results:

  • NUDT21 upregulation promotes OC malignant progression.
  • IGF2BP3 recruits NUDT21 to regulate SPTBN1 APA via m6A modification.
  • SPTBN1 short variant enhances OC oncogenicity, while the long variant inhibits tumor growth and metastasis by interacting with CDK1.

Conclusions:

  • A novel m6A-dependent regulatory pathway involving IGF2BP3, NUDT21, and SPTBN1 APA in OC was uncovered.
  • SPTBN1 isoforms exhibit opposing roles in OC.
  • This pathway presents potential therapeutic targets for ovarian cancer treatment.

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