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RNA拼接调节器EIF3D通过与免疫原相关的替代拼接在头部和部状细胞癌中调节瘤微环境
Dandan Lu1,2, Mijti Mihoayi1, Yimin Ablikim1
1Otolaryngology Diagnosis and Treatment Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, China.
Aging
|March 27, 2024
概括
细胞转化启动因子3亚单元D (EIF3D) 影响头部和部状细胞癌的瘤进展和免疫反应. 较低的EIF3D表达与更好的免疫治疗结果和预后相关.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 替代拼接 (AS) 显著影响瘤进展和瘤微环境 (TME).
- 在头部和部状细胞癌 (HNSC) 中,免疫原相关替代拼接 (IGAS) 的理解是有限的.
- 在癌症AS中的真核转化启动因子3亚单元D (EIF3D) 的作用需要进一步调查.
研究的目的:
- 研究EIF3D在HNSC中的功能和机制.
- 确定EIF3D表达与患者预后,免疫透和免疫治疗反应之间的关联.
- 阐明EIF3D在HNSC的替代拼接,特别是IGAS的监管中的作用.
主要方法:
- 使用TCGA SpliceSeq. 的生物信息学分析.
- 在体外细胞实验中,包括EIF3D在FadU细胞中的敲除.
- RNA测序 (RNA-seq) 用于分析基因表达和替代拼接事件.
主要成果:
- 在HNSC中高EIF3D表达与整体存活率 (OS) 和无进展存活率 (PFS) 较差有关.
- EIF3D敲除诱导了亡,并抑制了扩散,迁移和入侵.
- EIF3D影响了1923个替代拼接事件 (ASE),包括129个IGAS,并影响了52个差异表达免疫原体 (DEIG).
- 低EIF3D表达组显示出更高的免疫透率和更好的响应PD1/CTLA4免疫疗法.
结论:
- EIF3D是HNSC中异常替代拼接的关键调节器.
- EIF3D在HNSC进展和瘤微环境中发挥着重要作用.
- EIF3D是预测HNSC预后和免疫治疗反应的潜在生物标志物.
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