Abstract

miR-184-knockout mice display perturbed epidermal stem cell differentiation. However, the potential role of miR-184 in skin pathology is unclear. Here, we report that miR-184 controls epidermal stem cell dynamics and that miR-184 ablation enhances skin carcinogenesis in mice. In agreement, repression of miR-184 in human squamous cell carcinoma (SCC) enhances neoplastic hallmarks of human SCC cells in vitro and tumor development in vivo. Characterization of miR-184-regulatory network, suggests that miR-184 inhibits pro-oncogenic pathways, cell proliferation, and epithelial to mesenchymal transformation. Of note, depletion of miR-184 enhances the levels of β-catenin under homeostasis and following experimental skin carcinogenesis. Finally, the repression of β-catenin by miR-184, inhibits the neoplastic phenotype of SCC cells. Taken together, miR-184 behaves as an epidermal tumor suppressor, and may provide a potentially useful target for skin SCC therapy.

Details

Title
miR-184 represses β-catenin and behaves as a skin tumor suppressor
Author
Turovsky, Lubov 1 ; Kheshaiboun, Ghazal 1   VIAFID ORCID Logo  ; Yassen, Gharam 2 ; Nagosa, Sara 2 ; Boyango, Ilanit 3 ; Amitai-Lange, Aya 2 ; Bhattacharya, Swarnabh 2 ; Ilan, Neta 4 ; Vlodavsky, Israel 4 ; Aberdam, Daniel 5 ; Shalom-Feuerstein, Ruby 2   VIAFID ORCID Logo  ; Avitan-Hersh, Emily 6   VIAFID ORCID Logo 

1  Technion – Israel Institute of Technology, Department of Genetics & Developmental Biology, The Rappaport Faculty of Medicine & Research Institute, Technion Integrated Cancer Center, Haifa, Israel (GRID:grid.6451.6) (ISNI:0000 0001 2110 2151); Rambam Health Care Campus, Skin Cancer Research lab, Clinical research institute (CRIR), Haifa, Israel (GRID:grid.413731.3) (ISNI:0000 0000 9950 8111) 
2  Technion – Israel Institute of Technology, Department of Genetics & Developmental Biology, The Rappaport Faculty of Medicine & Research Institute, Technion Integrated Cancer Center, Haifa, Israel (GRID:grid.6451.6) (ISNI:0000 0001 2110 2151) 
3  Rambam Health Care Campus, Skin Cancer Research lab, Clinical research institute (CRIR), Haifa, Israel (GRID:grid.413731.3) (ISNI:0000 0000 9950 8111) 
4  Technion Israel Institute of Technology, Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Integrated Cancer Center, Haifa, Israel (GRID:grid.6451.6) (ISNI:0000 0001 2110 2151) 
5  Université de Paris Cité, INSERM U1138, Centre des Cordeliers, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602) 
6  Rambam Health Care Campus, Skin Cancer Research lab, Clinical research institute (CRIR), Haifa, Israel (GRID:grid.413731.3) (ISNI:0000 0000 9950 8111); Technion Israel Institute of Technology, Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Integrated Cancer Center, Haifa, Israel (GRID:grid.6451.6) (ISNI:0000 0001 2110 2151) 
Pages
174
Publication year
2024
Publication date
Feb 2024
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-024-06554-4
ProQuest document ID
3048753190
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.