The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma

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  • Veronica Stolearenco, University of Copenhagen
  • ,
  • Trine B Levring, University of Copenhagen
  • ,
  • Helene Myrtue Nielsen
  • Lise Lindahl
  • Simon Fredholm, University of Copenhagen
  • ,
  • Martin Kongsbak-Wismann, University of Copenhagen
  • ,
  • Andreas Willerslev-Olsen, University of Copenhagen
  • ,
  • Terkild B Buus, University of Copenhagen
  • ,
  • Claudia Nastasi, University of Copenhagen
  • ,
  • Tengpeng Hu, University of Copenhagen
  • ,
  • Maria Gluud, University of Copenhagen
  • ,
  • Christophe R M Côme, University of Copenhagen
  • ,
  • Thorbjørn Krejsgaard, University of Copenhagen
  • ,
  • Lars Iversen
  • Charlotte Menné Bonefeld, University of Copenhagen
  • ,
  • Kirsten Grønbæk, University of Copenhagen
  • ,
  • Özcan Met, University of Copenhagen
  • ,
  • Anders Woetmann, University of Copenhagen
  • ,
  • Niels Ødum, University of Copenhagen
  • ,
  • Carsten Geisler, University of Copenhagen

BACKGROUND: The thioredoxin-interacting protein (TXNIP) is involved in cellular metabolism and cell proliferation, and recently, deficient expression of TXNIP has been associated with progression and poor outcome for cancer patients.

OBJECTIVES: To assess TXNIP expression and function in malignant T cells from cutaneous T-cell lymphoma (CTCL).

METHODS: CTCL-derived malignant (MyLa2059, PB2B) and non-malignant (MyLa1850) cell lines were analysed by Western blotting and qPCR for TXNIP expression. Subsequently, the malignant CTCL cell lines were treated with GSK126 - an inhibitor of enhancer of zeste homolog 2 (EZH2) methyltransferase activity or assessed by bisulphite sequencing for TXNIP promoter methylation. Methylation was also assessed with the demethylating agent 5-azacytidine (5AZA). Finally, TXNIP was overexpressed in the malignant PB2B cell line via plasmid transduction, and the effect of TXNIP was further analysed by flow cytometry.

RESULTS: We report on low expression of TXNIP protein in all cell lines representing different subtypes and stages of CTCL when compared to non-malignant T cells. Epigenetic silencing and other mechanisms were involved in the repression of TXNIP whereas forced expression of TXNIP strongly inhibited proliferation of malignant T cells.

CONCLUSIONS: Epigenetic silencing and other as yet unknown mechanisms repress TXNIP expression in malignant T cells. As forced expression of TXNIP inhibits malignant proliferation, we propose that TXNIP is a putative tumour suppressor in CTCL.

Original languageEnglish
Pages (from-to)283-290
Number of pages8
Publication statusPublished - 2021

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