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Updated: Sep 11, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
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.
Abstract:
Conventional treatments for advanced endometriosis often have limited efficacy due to chemotherapy resistance, recurrence, and metastasis. This study analyzed clinical specimens to investigate the role of NXF1 in endometrial cancer (ECa) progression. Mouse models and molecular biology assays were used to elucidate NXF1's function and mechanisms in vitro and in vivo. Results showed NXF1 expression was negatively correlated with histological grade and poor patient prognosis. NXF1 inhibited ECa cell proliferation, colony formation, migration, and invasion in vitro, and suppressed tumor growth and metastasis in vivo. Mechanistically, NXF1 interferes with the binding of SRSF3 to exon 3 of SP4, preventing the formation of the "cancerous" long SP4 isoform (L-SP4) and promoting the "noncancerous" short SP4 isoform (S-SP4), which lacks the transactivation domain. In conclusion, NXF1 suppresses ECa tumorigenicity and progression through an SRSF3-mediated SP4 alternative splicing mechanism, and could serve as a novel prognostic biomarker for clinical intervention in ECa.
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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