The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma
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The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma. / Stolearenco, Veronica; Levring, Trine B; Nielsen, Helene Myrtue; Lindahl, Lise; Fredholm, Simon; Kongsbak-Wismann, Martin; Willerslev-Olsen, Andreas; Buus, Terkild B; Nastasi, Claudia; Hu, Tengpeng; Gluud, Maria; Côme, Christophe R M; Krejsgaard, Thorbjørn; Iversen, Lars; Bonefeld, Charlotte Menné; Grønbæk, Kirsten; Met, Özcan; Woetmann, Anders; Ødum, Niels; Geisler, Carsten.
In: Dermatology, Vol. 237, No. 2, 2021, p. 283-290.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma
AU - Stolearenco, Veronica
AU - Levring, Trine B
AU - Nielsen, Helene Myrtue
AU - Lindahl, Lise
AU - Fredholm, Simon
AU - Kongsbak-Wismann, Martin
AU - Willerslev-Olsen, Andreas
AU - Buus, Terkild B
AU - Nastasi, Claudia
AU - Hu, Tengpeng
AU - Gluud, Maria
AU - Côme, Christophe R M
AU - Krejsgaard, Thorbjørn
AU - Iversen, Lars
AU - Bonefeld, Charlotte Menné
AU - Grønbæk, Kirsten
AU - Met, Özcan
AU - Woetmann, Anders
AU - Ødum, Niels
AU - Geisler, Carsten
N1 - © 2020 S. Karger AG, Basel.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1159/000509159
DO - 10.1159/000509159
M3 - Journal article
C2 - 32799209
VL - 237
SP - 283
EP - 290
JO - Dermatology
JF - Dermatology
SN - 1018-8665
IS - 2
ER -
ID: 247510965