SATB1 in malignant T cells
Research output: Contribution to journal › Journal article › Research › peer-review
Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5, and its upstream activator Janus Kinase-3 (Jak3), triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic Jak3/STAT5/miR-155 pathway, SATB1, and cytokines linked to CTCL severity and progression indicating that SATB1 dysregulation is involved in CTCL pathogenesis.
Original language | English |
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Journal | The Journal of Investigative Dermatology |
Volume | 138 |
Issue number | 8 |
Pages (from-to) | 1805-1815 |
Number of pages | 11 |
ISSN | 0022-202X |
DOIs | |
Publication status | Published - 2018 |
ID: 197098365