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miR-181c regulates MCL1 and cell survival in GATA2 deficient cells
- Source :
- Journal of Leukocyte Biology. 111:805-816
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
Abstract
- GATA2 is a transcription factor critical for hematopoiesis. Germline mutations in GATA binding protein 2 (GATA2) led to haploinsufficiency, severe cytopenias of multiple cell lineages, susceptibility to infections and strong propensity to develop myelodysplastic syndrome, and acute myeloid leukemia. Mechanisms of progressive cytopenias remain unclear. MicroRNA (miRNA) represents a unique mechanism of post-transcriptional gene regulation. In this study, miRNA profiles were evaluated and eight miRNAs were found to be differentially expressed (≥2-fold, P ≤ 0.05) in patient-derived cell lines (N = 13) in comparison to controls (N = 10). miR-9, miR-181a-2-3p, miR-181c, miR-181c-3p, miR-486-3p, and miR-582 showed increased expression, whereas miR-223 and miR-424-3p showed decreased expression. Cell death assays indicated that miR-181c potently induces cell death in lymphoid (Ly-8 and SP-53) and myeloid (HL-60) cell lines. miR-181c was predicted to target myeloid cell leukemia (MCL)1, which was confirmed by transfection assays, resulting in significantly reduced MCL1 mRNA and decreased live cell numbers. Bone marrow analysis of 34 GATA2 patients showed significantly decreased cellularity, CD34-positive cells, monocytes, dendritic cells, NK cells, B cells, and B cell precursors in comparison to healthy controls (N = 29; P
- Subjects :
- Myeloid
Cell Survival
GATA2 Deficiency
Immunology
Cell
GATA2
Myeloid leukemia
Cell Biology
Transfection
Biology
medicine.disease
Molecular biology
GATA2 Transcription Factor
MicroRNAs
Haematopoiesis
Leukemia
medicine.anatomical_structure
medicine
Humans
Myeloid Cell Leukemia Sequence 1 Protein
Immunology and Allergy
B cell
Subjects
Details
- ISSN :
- 19383673 and 07415400
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- Journal of Leukocyte Biology
- Accession number :
- edsair.doi.dedup.....7920f9b341e1fc94ede21555f31bf763