Unilesional mycosis fungoides is associated with increased expression of microRNA-17~92 and T helper 1 skewing.


Journal

The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041

Informations de publication

Date de publication:
05 2019
Historique:
accepted: 08 11 2018
pubmed: 16 11 2018
medline: 1 8 2020
entrez: 16 11 2018
Statut: ppublish

Résumé

The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown. To investigate the microRNA profile in unilesional MF distinguishing it from early MF. Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA-binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively. Unilesional MF had a significantly higher level of expression of all members of the microRNA miR-17~92 cluster than early MF. Specifically, unilesional MF had a higher miR-17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR-17~92 members; higher gene expression of interleukin-2 and interferon-γ; and a statistically lower average percentage of GATA3 Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR-17~92 members along with Th1 skewing. These findings suggest a robust reactive T-cell immune response in unilesional MF and might account for the localized nature of this disease.

Sections du résumé

BACKGROUND
The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown.
OBJECTIVES
To investigate the microRNA profile in unilesional MF distinguishing it from early MF.
METHODS
Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA-binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively.
RESULTS
Unilesional MF had a significantly higher level of expression of all members of the microRNA miR-17~92 cluster than early MF. Specifically, unilesional MF had a higher miR-17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR-17~92 members; higher gene expression of interleukin-2 and interferon-γ; and a statistically lower average percentage of GATA3
CONCLUSIONS
Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR-17~92 members along with Th1 skewing. These findings suggest a robust reactive T-cell immune response in unilesional MF and might account for the localized nature of this disease.

Identifiants

pubmed: 30431147
doi: 10.1111/bjd.17425
doi:

Substances chimiques

CXCR3 protein, human 0
GATA3 Transcription Factor 0
GATA3 protein, human 0
MIR17HG, human 0
MicroRNAs 0
RNA, Long Noncoding 0
Receptors, CXCR3 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1123-1134

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2018 British Association of Dermatologists.

Auteurs

L Moyal (L)

Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

B Gorovitz-Haris (B)

Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

S Yehezkel (S)

Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

J Jacob-Hirsch (J)

Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel.

V Bershtein (V)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

A Barzilai (A)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel.

C Rotem (C)

Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

S Sherman (S)

Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

I Amitay-Laish (I)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

M Feinmesser (M)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

E Hodak (E)

Laboratory for Molecular Dermatology, Felsenstein Medical Research Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology and, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.

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Classifications MeSH