YY1通过负调控鼻咽癌中eIF4E的表达和翻译活性抑制肿瘤生长
YY1 Suppresses Tumor Growth by Negatively Regulating the Expression and Translation Activity of eIF4E in Nasopharyngeal Carcinoma.
文献信息
| PMID | 42938795 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Yumei Duan |
| 作者单位 | NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410078, China. |
| 期刊 | Cancers |
| SCI 分区 | Q2 |
| IF | 5.1 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 鼻咽癌 |
中文摘要
背景： 鼻咽癌（NPC）是一种复杂的恶性肿瘤，其进展的分子机制尚未完全阐明。真核翻译起始因子4E（eIF4E）是蛋白质合成的关键调控因子，在癌症中经常失调。我们此前已确定eIF4E是Yin Yang 1（YY1）的直接转录靶点，在该轴中YY1抑制NPC的侵袭和转移。方法：在此，我们研究了eIF4E在NPC生长中的功能及其与YY1的调控关系。使用CCK-8实验、克隆形成存活实验、Annexin V/碘化丙啶实验和异种移植模型来确定YY1/eIF4E在NPC生长中的作用；分别进行Western blotting和Co-IP以检查蛋白表达和蛋白-蛋白相互作用。结果：我们的研究结果表明，eIF4E有效促进NPC细胞增殖、加速细胞周期进程并抑制凋亡。此外，这些效应关键依赖于其丝氨酸209（S209）位点的磷酸化。此外，我们发现了一种新的调控机制，即YY1增强4E-BP1与eIF4E之间的关联，下调eIF4G表达，并与eIF4E和eIF4G之间相互作用减少相关，从而可能限制eIF4F复合物的形成。结论：本研究确立eIF4E磷酸化是NPC细胞生长和存活的致癌驱动因素，并确定YY1是负调控该轴的肿瘤抑制因子。这些见解将eIF4E定位为NPC干预的有前景且精确的治疗靶点。
英文摘要
Background: Nasopharyngeal carcinoma (NPC) is a complex malignancy, and the molecular mechanisms that drive its progression have not yet been fully elucidated. Eukaryotic translation initiation factor 4E (eIF4E), a pivotal regulator of protein synthesis, is frequently dysregulated in cancers. We previously identified eIF4E as a direct transcriptional target of Yin Yang 1 (YY1) in an axis where YY1 suppressed NPC invasion and metastasis. Methods: Here, we investigated the function of eIF4E in NPC growth and its regulatory relationship with YY1. The CCK-8 assay, clonogenic survival assay, Annexin V/propidium iodide assay, and xenograft models were used to determine the role of YY1/eIF4E in NPC growth; Western blotting and Co-IP were performed to examine protein expression and protein-protein interactions, respectively. Results: Our findings demonstrate that eIF4E potently promoted NPC cell proliferation, accelerated cell cycle progression, and inhibited apoptosis. Moreover, these effects were critically dependent on its phosphorylation at serine 209 (S209). Furthermore, we uncovered a novel regulatory mechanism whereby YY1 enhances the association between 4E-BP1 and eIF4E, downregulates eIF4G expression, and is associated with reduced interaction between eIF4E and eIF4G, thereby potentially limiting eIF4F complex formation. Conclusions: This study establishes eIF4E phosphorylation as an oncogenic driver of NPC cell growth and survival and identifies YY1 as a tumor suppressor that negatively regulates this axis. These insights position eIF4E as a promising and precise therapeutic target for NPC intervention.