SATB1 in malignant T cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Simon Mayland Fredholm
  • Linda Kubat
  • Sarah L. Mathiasen
  • Christina Friese
  • Edda Blümel
  • Tengpeng Hu
  • Lise M. Lindahl
  • Mariusz A. Wasik
  • Katharina Luise Maria Kopp
  • Sergei B. Koralov
  • Jenny L. Persson
  • Lars Iversen
  • Jürgen C. Becker

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.

OriginalsprogEngelsk
TidsskriftThe Journal of Investigative Dermatology
Vol/bind138
Udgave nummer8
Sider (fra-til)1805-1815
Antal sider11
ISSN0022-202X
DOI
StatusUdgivet - 2018

ID: 197098365