通过调节FOXO1-介导的SIRT1表达,LITAF抑制结直肠癌的干细胞和转移行为
Jiao Guan1,2, Zheng-Yun Zhang2, Jian-Hua Sun3
1Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Clinical & experimental metastasis
|June 2, 2023
概括
脂聚糖诱导瘤亡因子α因子 (LITAF) 在结直肠癌 (CRC) 中降低调控,抑制瘤的进展,转移和茎状. 恢复LITAF可能会为CRC提供一种新的治疗策略和预后生物标志物.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 脂聚糖诱导瘤亡因子α因子 (LITAF) 是一种转录因子,参与炎症反应,并在各种瘤中表现出抗癌性质.
- 在结直肠癌 (CRC) 进展中LITAF的具体作用及其潜在机制在很大程度上仍未被描述.
- 对癌症基因组图谱 (TCGA) 数据的全癌症分析显示,LITAF是CRC中显著下调的基因.
研究的目的:
- 研究LITAF在结直肠癌 (CRC) 组织中的表达特征及其与临床预后的相关性.
- 阐明LITAF在调节CRC细胞行为中的功能性作用,包括增殖,亡,迁移,入侵和干性.
- 探索LITAF影响CRC进展的分子机制,重点关注FOXO1-SIRT1信号轴.
主要方法:
- 利用公共数据库进行表达式分析和与预后相关联.
- 在CRC组织中使用qRT-PCR,西斑和免疫组织化学量化LITAF表达.
- 在CRC细胞和异种移植小鼠模型中进行了体外功能增益和功能丧失的研究.
主要成果:
- 在CRC组织中,LITAF的表达显著下调,并与预后不佳,病态晚期和肝转移有关.
- 过度表达LITAF抑制了CRC细胞的增殖,迁移,入侵和干细胞,同时在体外诱导了细胞亡.
- 在体内研究表明,LITAF抑制了瘤生长和肝转移,LITAF促进了FOXO1介导的SIRT1抑制,影响了癌症干和恶性表型.
结论:
- 在结直肠癌中,LITAF在表观遗传上被静止,并起到瘤抑制作用.
- 通过FOXO1-SIRT1通路抑制癌症干和恶性表型,LITAF抑制了CRC进展.
- LITAF代表了一个有前途的新型生物标志物,用于预测CRC预后,并可能成为治疗点.
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