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MiR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159879 | GEO | 2021/12/01

REPOSITORIES: GEO

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miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [sRNA-Seq]

Project description: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.

2021-12-01 | GSE159878 | GEO

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [RNA-Seq]

2021-12-01 | GSE159819 | GEO

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia

Project description:miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia

| PRJNA670710 | ENA

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [RNA-Seq]

Project description:miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [RNA-Seq]

| PRJNA670520 | ENA

miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [sRNA-Seq]

Project description:miR181a is a novel key player in the STAT3 mediated survival network of TCRab CD8+ T-LGL leukemia [sRNA-Seq]

| PRJNA670802 | ENA