دورية أكاديمية
MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2.
العنوان: | MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. |
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المؤلفون: | Gordino G; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Costa-Pereira S; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Corredeira P; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Alves P; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Costa L; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Medical Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal., Gomes AQ; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal., Silva-Santos B; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Ribot JC; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. |
المصدر: | EMBO reports [EMBO Rep] 2022 Jan 05; Vol. 23 (1), pp. e52234. Date of Electronic Publication: 2021 Nov 24. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2024- : [London] : Nature Publishing Group Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000- |
مواضيع طبية MeSH: | Cell Differentiation* , MicroRNAs*/genetics , Receptor, Notch2*/metabolism, T-Lymphocytes/*cytology, Humans ; Lymphocyte Activation ; MAP Kinase Kinase Kinase 2/metabolism ; Male ; Prostatic Neoplasms ; Signal Transduction |
مستخلص: | γδ T cells are a conserved population of lymphocytes that contributes to anti-tumor responses through its overt type 1 inflammatory and cytotoxic properties. We have previously shown that human γδ T cells acquire this profile upon stimulation with IL-2 or IL-15, in a differentiation process dependent on MAPK/ERK signaling. Here, we identify microRNA-181a as a key modulator of human γδ T cell differentiation. We observe that miR-181a is highly expressed in patients with prostate cancer and that this pattern associates with lower expression of NKG2D, a critical mediator of cancer surveillance. Interestingly, miR-181a expression negatively correlates with an activated type 1 effector profile obtained from in vitro differentiated γδ T cells and miR-181a overexpression restricts their levels of NKG2D and TNF-α. Upon in silico analysis, we identify two miR-181a candidate targets, Map3k2 and Notch2, which we validate via overexpression coupled with luciferase assays. These results reveal a novel role for miR-181a as critical regulator of human γδ T cell differentiation and highlight its potential for manipulation of γδ T cells in next-generation immunotherapies. (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.) |
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فهرسة مساهمة: | Keywords: cancer; effector T lymphocytes; miR-181a; microRNAs; γδ T cells |
المشرفين على المادة: | 0 (MIrn181 microRNA, human) 0 (MicroRNAs) 0 (NOTCH2 protein, human) 0 (Receptor, Notch2) EC 2.7.11.25 (MAP Kinase Kinase Kinase 2) EC 2.7.11.25 (MAP3K2 protein, human) |
تواريخ الأحداث: | Date Created: 20211125 Date Completed: 20220314 Latest Revision: 20231105 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC8728617 |
DOI: | 10.15252/embr.202052234 |
PMID: | 34821000 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1469-3178 |
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DOI: | 10.15252/embr.202052234 |