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

Summary: 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 assay...

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Main Authors: Nan Meng, Lingjun Li, Xueqin Yang, Hui Tang, Jizhong Wang, Songbai Zhang, Zongbao Xia, Jia Yao, Qi Zhang, Changrong Hu, Chunjie Su, Rui Duan
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225013744
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author Nan Meng
Lingjun Li
Xueqin Yang
Hui Tang
Jizhong Wang
Songbai Zhang
Zongbao Xia
Jia Yao
Qi Zhang
Changrong Hu
Chunjie Su
Rui Duan
author_facet Nan Meng
Lingjun Li
Xueqin Yang
Hui Tang
Jizhong Wang
Songbai Zhang
Zongbao Xia
Jia Yao
Qi Zhang
Changrong Hu
Chunjie Su
Rui Duan
author_sort Nan Meng
collection DOAJ
description Summary: 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.
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publishDate 2025-08-01
publisher Elsevier
record_format Article
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spelling doaj-art-41caaa3ba9ba4805a2aa75ff393fda032025-08-20T02:47:28ZengElsevieriScience2589-00422025-08-0128811311310.1016/j.isci.2025.113113NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicingNan Meng0Lingjun Li1Xueqin Yang2Hui Tang3Jizhong Wang4Songbai Zhang5Zongbao Xia6Jia Yao7Qi Zhang8Changrong Hu9Chunjie Su10Rui Duan11Jingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, China; Institute of Cancer Clinical Prevention and Control, Medical Department of Jingchu University of Technology, HuBei 448000, China; Corresponding authorJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaInstitute of Cancer Clinical Prevention and Control, Medical Department of Jingchu University of Technology, HuBei 448000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaSouth China University of Technology, Guangdong 510000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, ChinaJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, China; Corresponding authorJingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, HuBei 448000, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225013744CancerCell biologyMolecular biology
spellingShingle Nan Meng
Lingjun Li
Xueqin Yang
Hui Tang
Jizhong Wang
Songbai Zhang
Zongbao Xia
Jia Yao
Qi Zhang
Changrong Hu
Chunjie Su
Rui Duan
NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing
iScience
Cancer
Cell biology
Molecular biology
title NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing
title_full NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing
title_fullStr NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing
title_full_unstemmed NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing
title_short NXF1 suppresses progression of endometrial cancer by interacting with the SRSF3 to regulate SP4 splicing
title_sort nxf1 suppresses progression of endometrial cancer by interacting with the srsf3 to regulate sp4 splicing
topic Cancer
Cell biology
Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2589004225013744
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