MicroRNA-93 Targets p21 and Promotes Proliferation in Mycosis Fungoides T Cells
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
MicroRNA-93 Targets p21 and Promotes Proliferation in Mycosis Fungoides T Cells. / Gluud, Maria; Fredholm, Simon; Blümel, Edda; Willerslev-Olsen, Andreas; Buus, Terkild Brink; Nastasi, Claudia; Krejsgaard, Thorbjørn; Bonefeld, Charlotte Menné; Woetmann, Anders; Iversen, Lars; Litman, Thomas; Geisler, Carsten; Ødum, Niels; Lindahl, Lise M.
In: Dermatology, Vol. 237, 2021, p. 277–282.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - MicroRNA-93 Targets p21 and Promotes Proliferation in Mycosis Fungoides T Cells
AU - Gluud, Maria
AU - Fredholm, Simon
AU - Blümel, Edda
AU - Willerslev-Olsen, Andreas
AU - Buus, Terkild Brink
AU - Nastasi, Claudia
AU - Krejsgaard, Thorbjørn
AU - Bonefeld, Charlotte Menné
AU - Woetmann, Anders
AU - Iversen, Lars
AU - Litman, Thomas
AU - Geisler, Carsten
AU - Ødum, Niels
AU - Lindahl, Lise M.
PY - 2021
Y1 - 2021
N2 - Background: Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is a lymphoproliferative disorder characterized by proliferation of malignant T cells in a chronic inflammatory environment in the skin. The nature of MF is still not fully understood, but aberrant microRNA (miR) expression and function seem to play an important role in the pathogenesis and disease progression and have been proposed as a putative disease marker. Recent studies have reported aberrant expression of miR-93 in situin MF lesions and linked dysregulated miR-93 expression to advanced stages of MF. However, the pathophysiological role of miR-93 in MF is unknown. Objective: Here, we provide the first evidence that miR-93 targets the cell cycle regulator cyclin-dependent kinase inhibitor p21 and promotes growth of malignant T cells in MF. Methods/Results: Thus, inhibition of miR-93 in MF patient-derived malignant T-cell lines increases expression of p21 and inhibition of malignant proliferation. Notably, treatment with the histone deacetylase inhibitor Vorinostat (SAHA) reduces miR-93 expression and enhances p21 expression in the malignant T cells. Importantly, transfection with an miR-93 mimic partly blocks SAHA-induced p21 expression. Conclusions: we provide evidence that enhanced expression of the putative oncogenic miR, miR-93, represses the cell cycle inhibitor p21 and promotes proliferation of malignant T cells. Moreover, we demonstrate that SAHA triggers p21 expression - at least partly - through an inhibition of miR-93.
AB - Background: Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is a lymphoproliferative disorder characterized by proliferation of malignant T cells in a chronic inflammatory environment in the skin. The nature of MF is still not fully understood, but aberrant microRNA (miR) expression and function seem to play an important role in the pathogenesis and disease progression and have been proposed as a putative disease marker. Recent studies have reported aberrant expression of miR-93 in situin MF lesions and linked dysregulated miR-93 expression to advanced stages of MF. However, the pathophysiological role of miR-93 in MF is unknown. Objective: Here, we provide the first evidence that miR-93 targets the cell cycle regulator cyclin-dependent kinase inhibitor p21 and promotes growth of malignant T cells in MF. Methods/Results: Thus, inhibition of miR-93 in MF patient-derived malignant T-cell lines increases expression of p21 and inhibition of malignant proliferation. Notably, treatment with the histone deacetylase inhibitor Vorinostat (SAHA) reduces miR-93 expression and enhances p21 expression in the malignant T cells. Importantly, transfection with an miR-93 mimic partly blocks SAHA-induced p21 expression. Conclusions: we provide evidence that enhanced expression of the putative oncogenic miR, miR-93, represses the cell cycle inhibitor p21 and promotes proliferation of malignant T cells. Moreover, we demonstrate that SAHA triggers p21 expression - at least partly - through an inhibition of miR-93.
KW - Cutaneous T-cell lymphoma
KW - microRNA-93
KW - Mycosis fungoides
KW - p21
KW - SAHA/Vorinostat
KW - Tumor progression
U2 - 10.1159/000505743
DO - 10.1159/000505743
M3 - Journal article
C2 - 32335549
AN - SCOPUS:85084397053
VL - 237
SP - 277
EP - 282
JO - Dermatology
JF - Dermatology
SN - 1018-8665
ER -
ID: 243010897