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

doi:10.1159/000509159

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

11 Citations (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.

Original language	English
Journal	Dermatology
Volume	237
Issue number	2
Pages (from-to)	283-290
Number of pages	8
ISSN	1018-8665
DOIs	https://doi.org/10.1159/000509159
Publication status	Published - Mar 2021

Keywords

Cutaneous T-cell lymphoma
Epigenetic silencing
Thioredoxin-interacting protein
Tumour suppressor

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10.1159/000509159

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Stolearenco, V., Levring, T. B., Nielsen, H. M., Lindahl, L., Fredholm, S., Kongsbak-Wismann, M., Willerslev-Olsen, A., Buus, T. B., Nastasi, C., Hu, T., Gluud, M., Côme, C. R. M., Krejsgaard, T., Iversen, L., Bonefeld, C. M., Grønbæk, K., Met, Ö., Woetmann, A., Ødum, N., & Geisler, C. (2021). The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma. Dermatology, 237(2), 283-290. https://doi.org/10.1159/000509159

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 & Geisler, C 2021, 'The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma', Dermatology, vol. 237, no. 2, pp. 283-290. https://doi.org/10.1159/000509159

@article{98e04dc860944ac0a45ed684fa0c8fc5,

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

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.",

keywords = "Cutaneous T-cell lymphoma, Epigenetic silencing, Thioredoxin-interacting protein, Tumour suppressor",

author = "Veronica Stolearenco and Levring, \{Trine B\} and Nielsen, \{Helene Myrtue\} and Lise Lindahl and Simon Fredholm and Martin Kongsbak-Wismann and Andreas Willerslev-Olsen and Buus, \{Terkild B\} and Claudia Nastasi and Tengpeng Hu and Maria Gluud and C{\^o}me, \{Christophe Roger Michel\} and Thorbj{\o}rn Krejsgaard and Lars Iversen and Bonefeld, \{Charlotte Menn{\'e}\} and Kirsten Gr{\o}nb{\ae}k and {\"O}zcan Met and Anders Woetmann and Niels {\O}dum and Carsten Geisler",

note = "{\textcopyright} 2020 S. Karger AG, Basel.",

year = "2021",

month = mar,

doi = "10.1159/000509159",

language = "English",

volume = "237",

pages = "283--290",

journal = "Dermatology",

issn = "1018-8665",

publisher = "S. Karger AG",

number = "2",

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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 Roger Michel

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

PY - 2021/3

Y1 - 2021/3

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.

KW - Cutaneous T-cell lymphoma

KW - Epigenetic silencing

KW - Thioredoxin-interacting protein

KW - Tumour suppressor

UR - https://www.scopus.com/pages/publications/85090130715

U2 - 10.1159/000509159

DO - 10.1159/000509159

M3 - Journal article

C2 - 32799209

SN - 1018-8665

VL - 237

SP - 283

EP - 290

JO - Dermatology

JF - Dermatology

IS - 2

ER -

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

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