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缺少Setd2通过抑制SIRT1/FOXO通路促进胃瘤发生
Wenxin Feng1, Chunxiao Ma1, Hanyu Rao1
1State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
由于损失SETD2,SIRT1/FOXO通路受到损害,导致胃癌预后恶化. 这种表观遗传机制突出显示了SETD2作为胃癌 (GC) 患者的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 胃癌 (GC) 是全球癌症死亡的主要原因.
- SETD2是一种组胺甲基转移酶,在各种生物过程和瘤中起作用,但其在GC中的机制尚不清楚.
研究的目的:
- 研究SETD2在胃癌进展中的作用和机制.
- 为了确定SETD2缺乏是否预测胃癌的预后.
主要方法:
- 利用小鼠模型的胃特异性Setd2枯竭与c-MYC过度表达.
- 使用SGC7901细胞研究Setd2缺乏对增殖和迁移的影响.
- 研究了Sirt1和SIRT1/FOXO通路的表观遗传调节.
主要成果:
- Setd2 缺乏预测胃癌的预后不佳.
- 失去SETD2加速了由H. felis/MNU和c-Myc.诱导的胃瘤发生.
- Setd2 枯竭损害了 Sirt1 的表观遗传调节,抑制了 SIRT1/FOXO 途径.
- 恢复SIRT1/FOXO信号传输挽救了由Setd2缺陷引起的扩散和迁移缺陷.
结论:
- 通过SIRT1/FOXO通路,SETD2通过表观遗传调节胃瘤发生.
- 缺少SETD2与胃癌预后不佳有关.
- 针对SETD2-SIRT1/FOXO轴为胃癌提供了潜在的治疗策略.
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