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

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

8 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftDermatology
Vol/bind237
Udgave nummer2
Sider (fra-til)283-290
Antal sider8
ISSN1018-8665
DOI
StatusUdgivet - mar. 2021

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