Department of Cancer Biology; Department of Cell and Developmental Biology
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
Dicer is required for the maturation of microRNA, and loss of Dicer and miRNA processing has been found to alter numerous biological events during embryogenesis, including the development of mammalian skin and hair. We have previously examined the role of miRNA biogenesis in mouse embryonic fibroblasts and found that deletion of Dicer induces cell senescence regulated, in part, by the p53 tumor suppressor. Although Dicer and miRNA molecules are thought to have either oncogenic or tumor suppressing roles in various types of cancer, a role for Dicer and miRNAs in skin carcinogenesis has not been established. Here we show that perinatal ablation of Dicer in the skin of mice leads to loss of fur in adult mice, increased epidermal cell proliferation and apoptosis, and the accumulation of widespread DNA damage in epidermal cells. Co-ablation of Dicer and p53 did not alter the timing or extent of fur loss, but greatly reduced survival of Dicer-skin ablated mice, as these mice developed multiple and highly aggressive skin carcinomas. Our results describe a new mouse model for spontaneous basal and squamous cell tumorigenesis. Furthermore, our findings reveal that loss of Dicer in the epidermis induces extensive DNA damage, activation of the DNA damage response and p53-dependent apoptosis, and that Dicer and p53 cooperate to suppress mammalian skin carcinogenesis.
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© 2014 Lyle et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2014 Jun 30;9(6):e100920. doi: 10.1371/journal.pone.0100920. eCollection 2014. Link to article on publisher's site
Lyle S, Hoover K, Colpan C, Zhu Z, Matijasevic Z, Jones SN. (2014). Dicer cooperates with p53 to suppress DNA damage and skin carcinogenesis in mice. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1371/journal.pone.0100920. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/422
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