Meng Nan, Li Lingjun, Yang Xueqin, Tang Hui, Wang Jizhong, Zhang Songbai, Xia Zongbao, Yao Jia, Zhang Qi, Hu Changrong, Su Chunjie, Duan Rui
Jingmen 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.
iScience. 2025 Jul 22;28(8):113113. doi: 10.1016/j.isci.2025.113113. eCollection 2025 Aug 15.
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 and . Results showed NXF1 expression was negatively correlated with histological grade and poor patient prognosis. NXF1 inhibited ECa cell proliferation, colony formation, migration, and invasion , and suppressed tumor growth and metastasis . 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.
由于化疗耐药、复发和转移，晚期子宫内膜异位症的传统治疗方法往往疗效有限。本研究分析了临床标本，以探讨NXF1在子宫内膜癌（ECa）进展中的作用。使用小鼠模型和分子生物学实验来阐明NXF1的功能和机制。结果显示，NXF1表达与组织学分级及患者预后不良呈负相关。NXF1抑制ECa细胞增殖、集落形成、迁移和侵袭，并抑制肿瘤生长和转移。机制上，NXF1干扰SRSF3与SP4外显子3的结合，阻止“致癌性”长SP4异构体（L-SP4）的形成，并促进缺乏反式激活结构域的“非致癌性”短SP4异构体（S-SP4）的形成。总之，NXF1通过SRSF3介导的SP4可变剪接机制抑制ECa的致瘤性和进展，并可作为ECa临床干预的新型预后生物标志物。
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