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Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions

Year: 2025
Type: article
Abstract: The Janus kinase/signal transducers and activators of transcription (JAK-STAT) 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 induced-pluripotent 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-STAT 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-STAT 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.
Authors: Songyang Li, Yongjie Liu, Xiaofeng Yin, Yao Yang, Xinjia Liu, Jiaxing Qiu, Qinglan Yang, Yana Li, Zhiguo Tan, Hongyan Peng, Peiwen Xiong, Shuting Wu, Lanlan Huang, Xiangyu Wang, Sulai Liu, Yuxing Gong, Yuan Gao, Lingling Zhang, Junping Wang, Yafei Deng, Zhaoyang Zhong, Youcai Deng
Institutions: Central South University, Hunan Children's Hospital, Army Medical University, Chinese People's Liberation Army, University of South China, Columbia University, Hunan Normal University, Hunan Provincial People's Hospital, Shanxi Medical University, Anhui Medical University
Language: English
Subfield: Immunology
Open Access status: gold
Estimated APC paid: $2,600
Funders: Chongqing Municipal Education Commission Foundation, National Natural Science Foundation of China, Chongqing Science and Technology Commission, Natural Science Foundation of Hunan Province, Army Medical University, National Key Research and Development Program of China
Awards: G3060969416, G3334367173, G4014524702, G4150755819, G4194556540, G4911231509, G5048013358, G5598596144, G5678286846, G5748456603, G7130141877, G7588065135, G8314182351, G8370249571, G8852539686
OpenAlex ID: W4408083832
FWCI: 3.572
Cites: 43
Cited by: 12
Related to: 10