SATB1 in malignant T cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Simon Mayland Fredholm, Andreas Willerslev-Olsen, Özcan Met, Linda Kubat, Maria Gluud, Sarah L. Mathiasen, Christina Friese, Edda Blümel, David Leander Petersen, Tengpeng Hu, Claudia Nastasi, Lise M. Lindahl, Terkild Brink Buus, Thorbjørn Frej Krejsgaard, Mariusz A. Wasik, Katharina Luise Maria Kopp, Sergei B. Koralov, Jenny L. Persson, Charlotte Menne Bonefeld, Carsten Geisler & 4 andre Anders Woetmann Andersen, Lars Iversen, Jürgen C. Becker, Niels Ødum

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