1. Suppressed microRNA‐195‐5p expression in mycosis fungoides promotes tumor cell proliferation.
- Author
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Rittig, Anne H., Johansen, Claus, Celis, Pamela, Odum, Niels, Litman, Thomas, Woetmann, Anders, Lindahl, Lise M., and Iversen, Lars
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MYCOSIS fungoides ,CELL cycle regulation ,CELL proliferation ,CELL cycle ,CUTANEOUS T-cell lymphoma ,POLYMERASE chain reaction ,CELL cycle proteins - Abstract
Background: Several cancers, including mycosis fungoides (MF), have reported dysregulation of miR‐195‐5p. miR‐195‐5p plays a role in cell cycle regulation in several malignant diseases. Objectives: This study aimed to investigate: (a) the expression level of miR‐195‐5p in lesional MF skin biopsies and (b) the potential regulatory roles of miR‐195‐5p in MF. Methods: Quantitative real‐time polymerase chain reaction (RT‐qPCR) was used to determine miR‐195‐5p expression in MF skin biopsies and cell lines. The effect of miR‐195‐5p and ADP‐ribosylation factor‐like protein 2 (ARL2) on cell cycle and apoptosis was measured by flow cytometry assays. Changes in ARL2 expression were determined by RT‐qPCR and Western blotting (WB). Results: We found lower expression levels of miR‐195‐5p in lesional skin from MF patients compared with non‐lesional MF skin and skin from healthy volunteers. Additionally, miR‐195‐5p showed lower expression levels in the skin from patients with disease progression compared with patients with stable disease. In vitro studies showed that overexpression of miR‐195‐5p induced a cell cycle arrest in G0G1. Using microarray analysis, we identified several genes that were regulated after miR‐195‐5p overexpression. The most downregulated gene after miR‐195‐5p mimic transfection was ARL2. RT‐qPCR and WB analyses confirmed downregulation of ARL2 following transfection with miR‐195‐5p mimic. Lastly, transfection with siRNA against ARL2 also induced a G0G1 arrest. Conclusion: Upregulation of miR‐195‐5p in MF inhibits cycle arrest by downregulation of ARL2. miR‐195‐5p may thus function as a tumor suppressor in MF and low miR‐195‐5p expression in lesional MF skin may promote disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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