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 cell...
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Elsevier
2025-04-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221138352500111X |
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| author | 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 |
| author_facet | 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 |
| author_sort | Songyang Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a93d3ea240c641eebff68f6591fa6ddb |
| institution | OA Journals |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-a93d3ea240c641eebff68f6591fa6ddb2025-08-20T01:49:04ZengElsevierActa Pharmaceutica Sinica B2211-38352025-04-011541922193710.1016/j.apsb.2025.02.034Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functionsSongyang Li0Yongjie Liu1Xiaofeng Yin2Yao Yang3Xinjia Liu4Jiaxing Qiu5Qinglan Yang6Yana Li7Zhiguo Tan8Hongyan Peng9Peiwen Xiong10Shuting Wu11Lanlan Huang12Xiangyu Wang13Sulai Liu14Yuxing Gong15Yuan Gao16Lingling Zhang17Junping Wang18Yafei Deng19Zhaoyang Zhong20Youcai Deng21Pediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaDepartment of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing 400038, ChinaDepartment of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing 400038, China; Department of Pharmacy, the General Hospital of Western Theater Command of PLA, Chengdu 610083, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, China; The School of Pediatrics, Hengyang Medical School, University of South China (Hunan Children's Hospital), Changsha 410007, ChinaDepartment of Biological Sciences, Columbia University, NY 10027, USAPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaDepartment of Hepatobiliary Surgery, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha 410005, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, China; The School of Pediatrics, Hengyang Medical School, University of South China (Hunan Children's Hospital), Changsha 410007, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, ChinaDepartment of Hepatobiliary Surgery, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha 410005, ChinaTranslational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, ChinaTranslational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, ChinaInstitute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, ChinaState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing 400038, ChinaPediatrics Research Institute of Hunan Province, the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha 410007, China; Corresponding authors.The Fifth People's Hospital of Chongqing, Chongqing 400062, China; Corresponding authors.Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing 400038, China; State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing 400038, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S221138352500111XNK cellsiPSC-NK cellslncRNAmiR155HGCompeting endogenous RNAmiR-6756 |
| spellingShingle | 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 Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions Acta Pharmaceutica Sinica B NK cells iPSC-NK cells lncRNA miR155HG Competing endogenous RNA miR-6756 |
| title | Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions |
| title_full | Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions |
| title_fullStr | Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions |
| title_full_unstemmed | Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions |
| title_short | Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions |
| title_sort | identification of a jak stat mir155hg positive feedback loop in regulating natural killer nk cells proliferation and effector functions |
| topic | NK cells iPSC-NK cells lncRNA miR155HG Competing endogenous RNA miR-6756 |
| url | http://www.sciencedirect.com/science/article/pii/S221138352500111X |
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