miR-184 represses β-catenin and behaves as a skin tumor suppressor

Cell Death Dis. 2024 Feb 26;15(2):174. doi: 10.1038/s41419-024-06554-4.

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.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / pathology
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • MicroRNAs
  • MIRN184 microRNA, human
  • CTNNB1 protein, mouse
  • MIRN184 microRNA, mouse