Zhang, Ge and Fuchs have provided new insights into the role of microRNA-125b (miR-125b) in the initiation, progression and maintenance of squamous cell carcinoma (SCC). Using an inducible mouse model, they found that miR-125b overexpression in skin epithelium promoted spontaneous tumour formation as well as sensitizing skin to chemically-induced carcinogenesis. Furthermore, miR-125b expression maintained tumour growth by repressing differentiation and promoting a cancer stem-cell-like transcriptional programme. By identifying and validating miR-125b targets specifically associated with tumorigenesis, they found that miR-125b directly represses stress-responsive MAPK transcripts. It also indirectly maintains epidermal growth factor receptor (EGFR) signalling, by repressing vacuolar protein-sorting 4 homologue B (Vps4b), which encodes a protein that promotes endocytic degradation of phosphorylated EGFR.
References
Zhang, L. et al. miR-125b can enhance skin tumor initiation and promote malignant progression by repressing differentiation and prolonging cell survival. Genes Dev. 28, 2532–2546 (2014)
Rights and permissions
About this article
Cite this article
Villanueva, M. miRNAs — novel regulators in skin cancer. Nat Rev Cancer 15, 5 (2015). https://doi.org/10.1038/nrc3888
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrc3888