دورية أكاديمية
أعرض في EDS

miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia.

التفاصيل البيبلوغرافية
العنوان: miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia.
المؤلفون: Klusmann JH; Children's Hospital Boston, Massachusetts 02115, USA., Li Z, Böhmer K, Maroz A, Koch ML, Emmrich S, Godinho FJ, Orkin SH, Reinhardt D
المصدر: Genes & development [Genes Dev] 2010 Mar 01; Vol. 24 (5), pp. 478-90.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 8711660 Publication Model: Print Cited Medium: Internet ISSN: 1549-5477 (Electronic) Linking ISSN: 08909369 NLM ISO Abbreviation: Genes Dev Subsets: MEDLINE
أسماء مطبوعة: Publication: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory Press
Original Publication: [Cold Spring Harbor, N.Y.] : Cold Spring Harbor Laboratory in association with the Genetical Society of Great Britain, [c1987-
مواضيع طبية MeSH: Gene Expression Regulation, Leukemic*, Chromosomes, Human, Pair 21/*genetics , Leukemia, Megakaryoblastic, Acute/*metabolism , MicroRNAs/*metabolism, Animals ; Cell Differentiation/genetics ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Computational Biology ; DEAD-box RNA Helicases/genetics ; Down Syndrome/complications ; GATA1 Transcription Factor/genetics ; Gene Expression/genetics ; Gene Knockdown Techniques ; Humans ; K562 Cells ; Leukemia, Megakaryoblastic, Acute/complications ; Leukemia, Megakaryoblastic, Acute/genetics ; Megakaryocyte Progenitor Cells/cytology ; Megakaryocyte Progenitor Cells/metabolism ; Mice ; Mutation/genetics ; RNA Interference ; Repressor Proteins/genetics ; Ribonuclease III/genetics
مستخلص: Children with trisomy 21/Down syndrome (DS) are at high risk to develop acute megakaryoblastic leukemia (DS-AMKL) and the related transient leukemia (DS-TL). The factors on human chromosome 21 (Hsa21) that confer this predisposing effect, especially in synergy with consistently mutated transcription factor GATA1 (GATA1s), remain poorly understood. Here, we investigated the role of Hsa21-encoded miR-125b-2, a microRNA (miRNA) overexpressed in DS-AMKL/TL, in hematopoiesis and leukemogenesis. We identified a function of miR-125b-2 in increasing proliferation and self-renewal of human and mouse megakaryocytic progenitors (MPs) and megakaryocytic/erythroid progenitors (MEPs). miR-125b-2 overexpression did not affect megakaryocytic and erythroid differentiation, but severely perturbed myeloid differentiation. The proproliferative effect of miR-125b-2 on MEPs accentuated the Gata1s mutation, whereas growth of DS-AMKL/TL cells was impaired upon miR-125b repression, suggesting synergism during leukemic transformation in GATA1s-mutated DS-AMKL/TL. Integrative transcriptome analysis of hematopoietic cells upon modulation of miR-125b expression levels uncovered a set of miR-125b target genes, including DICER1 and ST18 as direct targets. Gene Set Enrichment Analysis revealed that this target gene set is down-regulated in DS-AMKL patients highly expressing miR-125b. Thus, we propose miR-125b-2 as a positive regulator of megakaryopoiesis and an oncomiR involved in the pathogenesis of trisomy 21-associated megakaryoblastic leukemia.
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معلومات مُعتمدة: R01 HL032259 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (GATA1 Transcription Factor)
0 (MIRN125 microRNA, human)
0 (MicroRNAs)
0 (Mirn125 microRNA, mouse)
0 (Repressor Proteins)
0 (ST18 protein, human)
EC 3.1.26.3 (DICER1 protein, human)
EC 3.1.26.3 (Ribonuclease III)
EC 3.6.4.13 (DEAD-box RNA Helicases)
تواريخ الأحداث: Date Created: 20100303 Date Completed: 20100317 Latest Revision: 20220316
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC2827843
DOI: 10.1101/gad.1856210
PMID: 20194440
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-5477
DOI:10.1101/gad.1856210