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SATB1 in Malignant T Cells

Fredholm, Simon; Willerslev-Olsen, Andreas; Met, Özcan; Kubat, Linda; Gluud, Maria; Mathiasen, Sarah L.; Friese, Christina; Blümel, Edda; Petersen, David L. and Hu, Tengpeng, et al. (2018) In Journal of Investigative Dermatology 138(8). p.1805-1815
Abstract

Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-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 microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and... (More)

Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-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 microRNA-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 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/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

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Journal of Investigative Dermatology
volume
138
issue
8
pages
1805 - 1815
publisher
Nature Publishing Group
external identifiers
  • scopus:85048705717
ISSN
0022-202X
DOI
10.1016/j.jid.2018.03.1526
language
English
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yes
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25cb7b7d-a496-4023-8517-8406b39fa9e5
date added to LUP
2018-07-03 10:22:50
date last changed
2019-02-03 05:33:40
@article{25cb7b7d-a496-4023-8517-8406b39fa9e5,
  abstract     = {<p>Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-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 microRNA-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 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/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.</p>},
  author       = {Fredholm, Simon and Willerslev-Olsen, Andreas and Met, Özcan and Kubat, Linda and Gluud, Maria and Mathiasen, Sarah L. and Friese, Christina and Blümel, Edda and Petersen, David L. and Hu, Tengpeng and Nastasi, Claudia and Lindahl, Lise M. and Buus, Terkild B. and Krejsgaard, Thorbjørn and Wasik, Mariusz A. and Kopp, Katharina L. and Koralov, Sergei B. and Persson, Jenny L. and Bonefeld, Charlotte M. and Geisler, Carsten and Woetmann, Anders and Iversen, Lars and Becker, Jürgen C. and Ødum, Niels},
  issn         = {0022-202X},
  language     = {eng},
  month        = {01},
  number       = {8},
  pages        = {1805--1815},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Investigative Dermatology},
  title        = {SATB1 in Malignant T Cells},
  url          = {http://dx.doi.org/10.1016/j.jid.2018.03.1526},
  volume       = {138},
  year         = {2018},
}