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通过调节RNF144A-FTO轴,FOXF2通过降低M2 TAMs来抑制食道状细胞癌
Tianci Han1, Wei Tong1, Junwei Xie1
1Department of Thoracic Surgery, Cancer Hospital of Dalian University of Technology, Shenyang 110042, China; Department of Thoracic Surgery, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.
International immunopharmacology
|October 24, 2024
概括
叉头盒F2 (FOXF2) 在食道状细胞癌 (ESCC) 中下调. 抑制FOXF2通过向FTO/RNF144A轴来抑制ESCC细胞的增殖和M2巨的偏离.
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:
- 食道状细胞癌 (ESCC) 具有高侵袭性和低生存率.
- 瘤相关巨细胞 (TAMs) 显著影响瘤进展,转移和免疫抑制.
- 叉头盒F2 (FOXF2),FOX家族的成员,在ESCC下调,其确切的作用和机制尚不清楚.
研究的目的:
- 研究FOXF2在ESCC进展中的作用及其与TAMs的相互作用.
- 阐明FOXF2在ESCC中的作用的基础分子机制.
主要方法:
- 在ESCC中的差异基因表达分析.
- 在ESCC细胞中,FOXF2的过度表达和沉默.
- 评估ESCC细胞增殖和TAM M2极化.
- 调查FOXF2,RNF144A和FTO之间的监管关系.
主要成果:
- 在ESCC组织中发现FOXF2的下调.
- 过度表达FOXF2抑制了ESCC细胞增殖和M2 TAM两极分化,而对FOXF2进行沉默则产生了相反的效果.
- 确定FOXF2可以促进RNF144A转录,从而导致FTO (m6A脱甲基酶) 的无化和降解.
- FTO过度表达抵消了FOXF2对TAM极化的影响.
结论:
- 通过抑制瘤细胞增殖和M2 TAM极化,FOXF2在缓解ESCC方面发挥着至关重要的作用.
- 该机制涉及FOXF2诱导的RNF144A转录,它针对FTO进行降解.
- FOXF2/RNF144A/FTO轴代表了ESCC治疗的潜在治疗目标.
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