SATB1 in Malignant T Cells

J Invest Dermatol. 2018 Aug;138(8):1805-1815. doi: 10.1016/j.jid.2018.03.1526. Epub 2018 May 8.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cohort Studies
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / immunology
  • Gene Knockdown Techniques
  • Humans
  • Interleukin-5 / immunology
  • Interleukin-5 / metabolism
  • Interleukin-9 / immunology
  • Interleukin-9 / metabolism
  • Janus Kinase 3 / metabolism
  • Matrix Attachment Region Binding Proteins / genetics*
  • Matrix Attachment Region Binding Proteins / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / immunology
  • MicroRNAs / metabolism*
  • Mycosis Fungoides / genetics*
  • Mycosis Fungoides / immunology
  • Mycosis Fungoides / pathology
  • Neoplasm Staging
  • RNA, Small Interfering / metabolism
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • IL5 protein, human
  • IL9 protein, human
  • Interleukin-5
  • Interleukin-9
  • MIRN155 microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • RNA, Small Interfering
  • SATB1 protein, human
  • STAT5 Transcription Factor
  • JAK3 protein, human
  • Janus Kinase 3