在膀癌中,MTHFD2通过激活JAK/STAT信号通路来促进PD-L1的表达
Linzhi Li1, Yunlong Zhang1, Weimin Hu1
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
Journal of cellular and molecular medicine
|July 22, 2023
概括
甲基酸酸脱酶2 (MTHFD2) 驱动膀癌 (BC) 的进展和免疫逃避. 向MTHFD2可能通过通过JAK/STAT通路抑制PD-L1表达提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 膀癌 (BC) 治疗面临着高复发率和进展率的挑战,尽管结合化学疗法.
- 新的治疗目标对于改善BC患者的治疗结果至关重要.
- 甲基基酸脱酶2 (MTHFD2) 涉及各种癌症的瘤发生和免疫逃避,但其在BC中的作用尚不清楚.
研究的目的:
- 为了研究MTHFD2在膀癌中的表达,预后意义和突功能.
- 阐明了MTHFD2在BC.中调高编程死亡配体1 (PD-L1) 表达的机制.
主要方法:
- 对MTHFD2表达和与BC.的临床特征和预后相关的公开数据库的分析.
- 在体外和体内实验中评估MTHFD2对BC细胞生长,迁移,入侵,瘤性和亡的影响.
- 调查MTHFD2表达,免疫透,PD-L1水平和Janus激酶/信号转换器和转录激活器 (JAK/STAT) 途径之间的相关性.
- 在干扰素马治疗和MTHFD2倒置后评估MTHFD2和PD-L1表达变化.
- 评估JAK/STAT通路激活对BC细胞中MTHFD2淘汰效应的影响.
主要成果:
- 在BC中的高MTHFD2表达与不良的临床特征和不良预后相关.
- MTHFD2促进BC细胞生长,迁移,入侵和瘤性,同时减少体外和体内细胞灭绝.
- MTHFD2的表达与免疫透的增加,PD-L1水平的升高以及BC中JAK/STAT通路的激活有关.
- 干扰素马治疗可提高MTHFD2,PD-L1和JAK/STAT通路蛋白质的调节,而MTHFD2倒置可降低它们的表达.
- JAK/STAT通路的激活部分抵消了MTHFD2敲击对BC细胞的影响.
结论:
- MTHFD2在膀癌中起着重要的突性作用.
- MTHFD2通过上调PD-L1表达来促进BC进展和免疫逃避.
- 通过JAK/STAT信号通路的激活,PD-L1的MTHFD2介导的上调发生.
- MTHFD2代表了膀癌治疗的潜在治疗标.
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