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

8 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

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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 -

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

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