摘要
The Janus kinase/signal transducers and activators of transcription(JAK-TAT)control natural killer(NK)cells development and cytotoxic functions,however,whether long non-coding RNAs(lncRNAs)are involved in this pathway remains unknown.We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and inducedpluripotent stem cells(iPSCs)-derived NK(iPSC-NK)cells,without reliance on its derived miR-155 and micropeptide P155.Mechanistically,miR155HG bound to miR-6756 and relieved its repression of JAK3 expression,thereby promoting the JAK-TAT pathway and enhancing NK cell proliferation and function.Further investigations disclosed that upon cytokine stimulation,STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription.Collectively,we identify a miR155HG-mediated positive feedback loop of the JAK-TAT signaling.Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer,especially iPSC-derived NK cells.
基金
supported by funding from the National Key Research and Development Project(2020YFA0113500,China)
Hunan Provincial Natural Science Foundation of China(2023JJ40341,2023JJ40352)
National Natural Science Foundation of China(82473934,32100616,32100490,81922068,82304510,82304511)
Chongqing Science and Technology Commission of China(cstc2021jcyj-jqX0006)
Scientific Research Project of Hunan Provincial Health Commission(A202302077875,B202302078452,China)
the projects of Army Medical University(2022XJS06,2023XQN20,2023XQN19,China)
Chongqing Municipal Education Commission Foundation(KJZD-M202412802,China)
the Natural Science Foundation of Changsha,Hunan Province(kq2208087,China)
the special fund of the Hunan provincial key laboratory of pediatric orthopedics(No.2023TP1019,China)。
