1. The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma.
- Author
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Stolearenco V, Levring TB, Nielsen HM, Lindahl L, Fredholm S, Kongsbak-Wismann M, Willerslev-Olsen A, Buus TB, Nastasi C, Hu T, Gluud M, Côme CRM, Krejsgaard T, Iversen L, Bonefeld CM, Grønbæk K, Met Ö, Woetmann A, Ødum N, and Geisler C
- Subjects
- Cell Line, Tumor, Cell Proliferation, DNA Methylation, Enhancer of Zeste Homolog 2 Protein antagonists & inhibitors, Enzyme Inhibitors pharmacology, Epigenesis, Genetic, Gene Silencing, Humans, Indoles pharmacology, Promoter Regions, Genetic, Pyridones pharmacology, Carrier Proteins genetics, Carrier Proteins metabolism, Lymphoma, T-Cell, Cutaneous pathology, Skin Neoplasms pathology
- 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., (© 2020 S. Karger AG, Basel.)
- Published
- 2021
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