The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Dermatology |
Vol/bind | 237 |
Udgave nummer | 2 |
Sider (fra-til) | 283-290 |
Antal sider | 8 |
ISSN | 1018-8665 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
© 2020 S. Karger AG, Basel.
ID: 247510965