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Series GSE159819 Query DataSets for GSE159819
Status Public on Dec 01, 2021
Title miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary TCRαβ CD8 large granular lymphocyte (LGL) leukemia is a rare heterogeneous hematological disorder with a chronic disease course that mostly affects elderly. It is generally accepted that LGL cells arise as a consequence of chronic antigenic stimulation and inflammation and thrive because of dysregulation of mainly the STAT3 but also to some extent the ERK pathway, which are constitutively activated. In approximately 40% of patients this is due to STAT3 activating mutations, but for the other 60% it remains to be elucidated, why the STAT3 pathway is chronically activated. miRNAs are one of the most potent regulators in health and disease and are also linked with various leukemias. Therefore, we hypothesized that aberrant miRNA expression could contribute to dysregulation of the STAT3 pathway. miRNA sequencing in LGL leukemia cases and aged-matched healthy control TEMRA cells revealed overexpression of miRNA181a. Furthermore, gene set enrichment analysis (GSEA) of miRNA181a implicated its involvement in the STAT3 and ERK1/2 pathways. Phosphoflow analysis of STAT3, ERK1/2 in miR181a-transfected human CD8 T cells revealed that miR181a overexpression results in STAT3 and ERK1/2 phosphorylation. By using TL1, a human T-LGL cell line model, we have now established that miR181a is the common actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition in LGL leukemia patients. Additionally, miR181a induces ERK1/2 phosphorylation by inhibition of DUSP6. Taken together, our data show that miR181a is the missing link to explain why STAT3-unmutated patients show hyperactive STAT3.
 
Overall design mRNA sequencing of T-LGL patients compared to healthy control TEMRA CD8+ T cells
 
Contributor(s) Langerak AW, Assmann JL, Leon LG
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Submission date Oct 21, 2020
Last update date Dec 01, 2021
Contact name Anton W Langerak
E-mail(s) a.langerak@erasmusmc.nl
Organization name ErasmusMC
Department Immunology
Lab Laboratory of Medical Immunology
Street address Dr. Molewaterplein 40
City Rotterdam
State/province Zuid Holland
ZIP/Postal code 3015 GD
Country Netherlands
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM4848004 JA1_B80_control
GSM4848005 JA2_B81_control
GSM4848006 JA3_B86_control
This SubSeries is part of SuperSeries:
GSE159879 miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia
Relations
BioProject PRJNA670520
SRA SRP288061

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE159819_LGL_ftc_evenmoreclean.counts.txt.gz 437.0 Kb (ftp)(http) TXT
GSE159819_LGL_ftc_evenmoreclean.csv.gz 437.0 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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