Suppressed microRNA-195-5p expression in mycosis fungoides promotes tumor cell proliferation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Suppressed microRNA-195-5p expression in mycosis fungoides promotes tumor cell proliferation. / Rittig, Anne H.; Johansen, Claus; Celis, Pamela; Odum, Niels; Litman, Thomas; Woetmann, Anders; Lindahl, Lise M.; Iversen, Lars.
In: Experimental Dermatology, Vol. 30, No. 8, 2021, p. 1141-1149.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Suppressed microRNA-195-5p expression in mycosis fungoides promotes tumor cell proliferation
AU - Rittig, Anne H.
AU - Johansen, Claus
AU - Celis, Pamela
AU - Odum, Niels
AU - Litman, Thomas
AU - Woetmann, Anders
AU - Lindahl, Lise M.
AU - Iversen, Lars
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - ARL2
KW - cancer
KW - cell cycle arrest
KW - cutaneous T-cell lymphoma
KW - microarray
KW - microRNA
KW - proliferation
KW - tumor suppressor
U2 - 10.1111/exd.14124
DO - 10.1111/exd.14124
M3 - Journal article
C2 - 32492224
AN - SCOPUS:85087170444
VL - 30
SP - 1141
EP - 1149
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 8
ER -
ID: 244612350