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

IF 14.7 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI:10.1016/j.apsb.2025.02.034

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 , Youcai Deng

{"title":"Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions","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 , Youcai Deng","doi":"10.1016/j.apsb.2025.02.034","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1922-1937"},"PeriodicalIF":14.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Pharmaceutica Sinica. B","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S221138352500111X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

JAK-STAT-miR155HG正反馈环调控自然杀伤细胞增殖及其效应功能的鉴定

Janus激酶/信号转导和转录激活因子（JAK-STAT）控制自然杀伤（NK）细胞的发育和细胞毒性功能，然而，长链非编码rna （lncRNAs）是否参与这一途径尚不清楚。我们发现miR155HG在活化的NK细胞中升高，并在NK92和诱导多能干细胞（iPSCs）衍生的NK （iPSC-NK）细胞中促进其增殖和效应功能，而不依赖于其衍生的miR-155和微肽P155。在机制上，miR155HG与miR-6756结合，解除其对JAK3表达的抑制，从而促进JAK-STAT通路，增强NK细胞的增殖和功能。进一步研究发现，在细胞因子刺激下，STAT3直接与miR155HG启动子相互作用，诱导miR155HG转录。总之，我们确定了mir155hg介导的JAK-STAT信号的正反馈回路。我们的研究也将在NK细胞过继性转移治疗领域，特别是ipsc来源的NK细胞，为改善NK细胞的生成和效应功能提供一个关于miR155HG的有力靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Pharmaceutica Sinica. B Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

22.40

自引率

5.50%

发文量

1051

审稿时长

19 weeks

期刊介绍： The Journal of the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association oversees the peer review process for Acta Pharmaceutica Sinica. B (APSB). Published monthly in English, APSB is dedicated to disseminating significant original research articles, rapid communications, and high-quality reviews that highlight recent advances across various pharmaceutical sciences domains. These encompass pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis, and pharmacokinetics. A part of the Acta Pharmaceutica Sinica series, established in 1953 and indexed in prominent databases like Chemical Abstracts, Index Medicus, SciFinder Scholar, Biological Abstracts, International Pharmaceutical Abstracts, Cambridge Scientific Abstracts, and Current Bibliography on Science and Technology, APSB is sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association. Its production and hosting are facilitated by Elsevier B.V. This collaborative effort ensures APSB's commitment to delivering valuable contributions to the pharmaceutical sciences community.