Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions
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
- Xiaofeng Yin (ORCID: https://orcid.org/0009-0004-5244-5164)
- Yuan Gao (ORCID: https://orcid.org/0000-0002-0670-9104)
- Jingyi Qiu (ORCID: https://orcid.org/0000-0002-1290-8812)
- Qinglan Yang (ORCID: https://orcid.org/0009-0004-7672-511X)
- Songyang Li (ORCID: https://orcid.org/0009-0000-6264-2832)
- Yafei Deng (ORCID: https://orcid.org/0009-0008-1940-8336)
- Zhaoyang Zhong (ORCID: https://orcid.org/0000-0002-2338-038X)
- Xiangyu Wang (ORCID: https://orcid.org/0000-0001-5397-1909)
- Youcai Deng (ORCID: https://orcid.org/0000-0001-5488-8576)
- Hongyan Peng (ORCID: https://orcid.org/0009-0005-9094-7664)
- Sulai Liu (ORCID: https://orcid.org/0000-0002-5257-3922)
- Lanlan Huang (ORCID: https://orcid.org/0009-0009-4376-520X)
- Lingling Zhang (ORCID: https://orcid.org/0000-0003-4410-8542)
- Junping Wang (ORCID: https://orcid.org/0000-0001-5905-0940)
- Yongjie Liu (ORCID: https://orcid.org/0000-0003-1812-109X)
- Yana Li (ORCID: https://orcid.org/0000-0002-8479-3292)
- Peiwen Xiong (ORCID: https://orcid.org/0000-0002-8346-9132)
- Yang Yao (ORCID: https://orcid.org/0000-0003-2122-0136)
- Shuting Wu
- Yuxing Gong
- Xinjia Liu
- Zhiguo Tan (ORCID: https://orcid.org/0009-0001-7318-5910)
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Central South University (CN)
- Army Medical University (CN)
- Hunan Normal University (CN)
- Shanxi Medical University (CN)
- Anhui Medical University (CN)
- Chengdu Military General Hospital (CN)
- Hunan Children's Hospital (CN)
- First People's Hospital of Chongqing (CN)
- Columbia University (US)
- University of South China (CN)
Publication Details
- Journal
- Acta Pharmaceutica Sinica B
- Published
- 2025-03-02
- DOI
- https://doi.org/10.1016/j.apsb.2025.02.034
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.19