Elevated exosome-transferrable lncRNA EPB41L4A-AS1 in CD56bright NK cells is responsible for the impaired NK function in neuroblastoma patients by suppressing cell glycolysis.

Abstract

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 CD56bright 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 CD56bright NK subset. The inhibitory function of lncRNA EPB41L4A-AS1 was recapitulated. Interestingly, our study demonstrated that exosomal lncRNA EPB41L4A-AS1 was transferrable from CD56bright NK to CD56dim 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 CD56bright NK subset and a cross-talk between heterogeneous NK subsets was achieved by transferring metabolic inhibitory lncRNA through exosomes.

• Authors: Wenjia Chai, Xiaolin Wang, Zhengjing Lu, Shihan Zhang, Wei Wang, Hui Wang, Chenghao Chen, Wei Yang, Haiyan Cheng, Huanmin Wang, Jun Feng, Shen Yang, Qiliang Li, Wenqi Song, Fang Jin, Hui Zhang, Yan Su, Jingang Gui
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 250 Pg. 109322 (05 2023) ISSN: 1521-7035 [Electronic] United States
• PMID: 37024023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• CD56 Antigen
• RNA, Long Noncoding
• NCAM1 protein, human

Topics

• Humans
• CD56 Antigen
• Exosomes (metabolism)
• Glycolysis
• Killer Cells, Natural
• Neuroblastoma (genetics)
• RNA, Long Noncoding (genetics, metabolism)