SMURF1调节CTCF-HOXA10轴并促进鼻咽癌的肿瘤进展。
SMURF1 Regulates CTCF-HOXA10 Axis and Promotes Tumor Progression in Nasopharyngeal Carcinoma.
摘要(中文译文)
同源框A10（HOXA10）的异常上调与鼻咽癌（NPC）的进展有关，但其上调机制尚未完全阐明。本研究表明，E3泛素连接酶SMAD泛素化调节因子1（SMURF1）促进泛素介导的CCCTC结合因子（CTCF）的降解，从而减轻CTCF介导的HOXA10转录抑制。因此，HOXA10表达的升高有助于鼻咽癌的肿瘤进展。我们证实HOXA10在鼻咽癌中显著上调，并促进鼻咽癌细胞的恶性表型。CTCF被鉴定为HOXA10的直接转录抑制因子，在鼻咽癌中下调。此外，发现SMURF1在NPC中增加，它直接与CTCF结合并调节其蛋白质稳定性。具体来说，SMURF1促进了与K48相关的CTCF泛素化降解。体外功能检测显示，SMURF1敲除抑制鼻咽癌细胞增殖、迁移、侵袭和上皮间质转化。体内实验进一步证实，SMURF1敲低抑制了NPC肿瘤的生长和肺转移，同时肿瘤和肺组织中CTCF表达增加，HOXA10水平降低。总的来说，这些发现揭示了SMURF1/CTCF/HOXA10轴是鼻咽癌发病机制中的关键机制，将SMURF1定位为有前景的干预治疗靶点。
Abstract
The aberrant upregulation of Homeobox A10 (HOXA10) has been implicated in the progression of nasopharyngeal carcinoma (NPC), but the mechanisms driving its upregulation are not fully elucidated. This study demonstrated that the E3 ubiquitin ligase SMAD ubiquitination regulatory factor 1 (SMURF1) promoted the ubiquitin-mediated degradation of CCCTC-binding factor (CTCF), thereby alleviating CTCF-mediated transcriptional repression on HOXA10. Consequently, elevated HOXA10 expression contributed to tumor progression in NPC. We confirmed that HOXA10 was significantly upregulated in NPC and promoted malignant phenotypes of NPC cells. CTCF was identified as a direct transcriptional repressor of HOXA10 and was downregulated in NPC. Moreover, SMURF1 was found to be increased in NPC, where it directly bound to CTCF and regulated its protein stability. Specifically, SMURF1 promoted K48-linked ubiquitination degradation of CTCF. In vitro functional assays revealed that SMURF1 knockdown inhibited NPC cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In vivo experiments further confirmed that SMURF1 knockdown suppressed NPC tumor growth and lung metastasis, accompanied by increased CTCF expression and decreased HOXA10 level in both tumor and lung tissues. Collectively, these findings revealed the SMURF1/CTCF/HOXA10 axis as a crucial mechanism in NPC pathogenesis, positioning SMURF1 as a promising therapeutic target for intervention.
如何引用
AMA
Ying Jin, Tian Zhang, Zhimin Wu, Yuanshan Liang, Yiting Jiang, Guodong Yu. SMURF1 Regulates CTCF-HOXA10 Axis and Promotes Tumor Progression in Nasopharyngeal Carcinoma.. Cancer science. 2026; doi:10.1111/cas.70353.
APA
Ying Jin, Tian Zhang, Zhimin Wu, Yuanshan Liang, Yiting Jiang, Guodong Yu (2026). SMURF1 Regulates CTCF-HOXA10 Axis and Promotes Tumor Progression in Nasopharyngeal Carcinoma.. Cancer science. https://doi.org/10.1111/cas.70353
GB/T 7714
Ying Jin, Tian Zhang, Zhimin Wu, Yuanshan Liang, Yiting Jiang, Guodong Yu. SMURF1 Regulates CTCF-HOXA10 Axis and Promotes Tumor Progression in Nasopharyngeal Carcinoma.[J]. Cancer science, 2026 doi:10.1111/cas.70353.
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