MicroRNA-93 Targets p21 and Promotes Proliferation in Mycosis Fungoides T Cells
| Autor: | Niels Ødum, Edda Blümel, Thorbjørn Krejsgaard, Simon Fredholm, Terkild B. Buus, Claudia Nastasi, Anders Woetmann, Andreas Willerslev-Olsen, Lars Iversen, Carsten Geisler, Maria Gluud, Charlotte M. Bonefeld, Lise M. Lindahl, Thomas Litman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Mycosis fungoides Skin Neoplasms medicine.drug_class Cutaneous T-cell lymphoma RNA Messenger/metabolism Gene Expression Antineoplastic Agents Dermatology Gene Expression/drug effects Biology Skin Neoplasms/pathology Cell Proliferation/drug effects 030207 dermatology & venereal diseases 03 medical and health sciences Mycosis Fungoides 0302 clinical medicine Cell Line Tumor microRNA medicine Humans RNA Messenger Vorinostat MicroRNAs/antagonists & inhibitors Cell Proliferation microRNA-93 p21 Histone deacetylase inhibitor Cyclin-Dependent Kinase Inhibitor p21/genetics Transfection Cell cycle medicine.disease SAHA/Vorinostat Tumor progression Histone Deacetylase Inhibitors Mycosis Fungoides/pathology MicroRNAs 030220 oncology & carcinogenesis Cancer research Antineoplastic Agents/pharmacology Histone Deacetylase Inhibitors/pharmacology Vorinostat/pharmacology medicine.drug |
| Zdroj: | Gluud, M, Fredholm, S, Blümel, E, Willerslev-Olsen, A, Buus, T B, Nastasi, C, Krejsgaard, T, Bonefeld, C M, Woetmann, A, Iversen, L, Litman, T, Geisler, C, Ødum, N & Lindahl, L M 2021, ' MicroRNA-93 Targets p21 and Promotes Proliferation in Mycosis Fungoides T Cells ', Dermatology, vol. 237, no. 2, pp. 277-282 . https://doi.org/10.1159/000505743 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|