RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD56(bright) NK 细胞中升高的可经外泌体转移的 lncRNA EPB41L4A-AS1 通过抑制细胞糖酵解导致神经母细胞瘤患者 NK 功能受损
英文原题：Elevated exosome-transferrable lncRNA EPB41L4A-AS1 in CD56(bright) NK cells is responsible for the impaired NK function in neuroblastoma patients by suppressing cell glycolysis.
查看英文原题
Elevated exosome-transferrable lncRNA EPB41L4A-AS1 in CD56(bright) NK cells is responsible for the impaired NK function in neuroblastoma patients by suppressing cell glycolysis.
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中文摘要
NK 细胞是神经母细胞瘤（NB）免疫监视和清除的关键免疫组分之一。葡萄糖代谢作为 NK 激活的主要燃料来源受到精细调控。
我们的数据显示，NB 中 NK 激活减弱，同时 CD56 bright 亚群不成比例地增加。进一步研究表明，NB 中的 NK 细胞呈现糖酵解停滞，并伴随 CD56 bright NK 亚群中长链非编码 RNA（lncRNA）EPB41L4A-AS1 表达升高，该 lncRNA 是已知的糖酵解调控关键参与者。lncRNA EPB41L4A-AS1 的抑制功能得到了重现。有趣的是，我们的研究表明，外泌体 lncRNA EPB41L4A-AS1 可从 CD56 bright NK 转移至 CD56 dim NK，并能够抑制靶 NK 的糖酵解。
我们的数据表明，患者 NK 细胞中的糖酵解停滞与 CD56 bright NK 亚群中 lncRNA 升高相关，而异质性 NK 亚群之间的交互是通过外泌体转移代谢抑制性 lncRNA 实现的。
展开英文摘要原文
NK cells are one of key immune components in neuroblastoma (NB) surveillance and eradication. Glucose metabolism as a major source of fuel for NK activation is exquisitely regulated.
Our data revealed a diminished NK activation and a disproportionally augmented CD56 bright subset in NB.
Further study showed that NK cells in NB presented with an arrested glycolysis accompanied by an elevated expression of the long noncoding RNA (lncRNA) EPB41L4A-AS1, a known crucial participant in glycolysis regulation, in the CD56 bright NK subset. The inhibitory function of lncRNA EPB41L4A-AS1 was recapitulated. Interestingly, our study demonstrated that exosomal lncRNA EPB41L4A-AS1 was transferrable from CD56 bright NK to CD56 dim NK and was able to quench the glycolysis of target NK.
Our data demonstrated that an arrested glycolysis in patient NK cells was associated with an elevated lncRNA in CD56 bright NK subset and a cross-talk between heterogeneous NK subsets was achieved by transferring metabolic inhibitory lncRNA through exosomes.
论文信息
- 作者
- Chai W、Wang X、Lu Z、Zhang S、Wang W、Wang H、Chen C、Yang W
- 第一作者单位
- Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China.China
- 通讯作者单位
- Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China. Electronic address: guijingang@bch.com.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Clinical immunology (Orlando, Fla.)2023 May
- 原文标识
- PubMed 37024023 · DOI 10.1016/j.clim.2023.109322