NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing

Nan Meng1,2, Lingjun Li1, Xueqin Yang2

  • 1Jingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, China.

Iscience
|August 12, 2025
PubMed

Insights

Nuclear export factor 1 (NXF1) suppresses endometrial cancer (ECa) progression by regulating SP4 alternative splicing. This finding offers a potential new biomarker for ECa treatment and prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Advanced endometriosis treatments face challenges with chemotherapy resistance, recurrence, and metastasis.
  • The role of Nuclear Factor X-interacting protein 1 (NXF1) in endometrial cancer (ECa) progression requires further investigation.

Purpose of the Study:

  • To investigate the function and molecular mechanisms of NXF1 in endometrial cancer (ECa) progression.
  • To determine if NXF1 can serve as a prognostic biomarker for ECa.

Main Methods:

  • Analysis of clinical endometrial cancer specimens.
  • In vitro and in vivo experiments using mouse models and molecular biology assays.
  • Investigation of NXF1's interaction with SRSF3 and SP4 splicing.

Main Results:

  • NXF1 expression inversely correlated with histological grade and patient prognosis.
  • NXF1 inhibited ECa cell proliferation, colony formation, migration, and invasion in vitro.
  • NXF1 suppressed tumor growth and metastasis in vivo by promoting the short SP4 isoform (S-SP4) over the long SP4 isoform (L-SP4) via an SRSF3-mediated mechanism.

Conclusions:

  • NXF1 acts as a tumor suppressor in endometrial cancer (ECa).
  • NXF1 inhibits ECa tumorigenicity and progression through an SRSF3-mediated SP4 alternative splicing mechanism.
  • NXF1 holds potential as a novel prognostic biomarker for clinical intervention in ECa.

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