دورية أكاديمية
The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia.
| العنوان: | The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia. |
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| المؤلفون: | Chao Shen, Ming-Tai Chen, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Rui Su, Hai-Shuang Lin, Li Song, Fang Wang, Yan-Ni Ma, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang |
| المصدر: | PLoS Genetics, Vol 12, Iss 9, p e1006259 (2016) |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | Genetics, QH426-470 |
| الوصف: | MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7390 1553-7404 |
| Relation: | http://europepmc.org/articles/PMC5019412?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404 |
| DOI: | 10.1371/journal.pgen.1006259 |
| URL الوصول: | https://doaj.org/article/568df2fe6e5249549d4c36310c3dccfd |
| رقم الأكسشن: | edsdoj.568df2fe6e5249549d4c36310c3dccfd |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537390 15537404 |
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| DOI: | 10.1371/journal.pgen.1006259 |