Author Response: Loss of Dnmt3a and Dnmt3b Does Not Affect Epidermal Homeostasis but Promotes Squamous Transformation Through PPAR-γ
March 2017
Studysummary This study found that loss of the DNA methyltransferase Dnmt3a, but not Dnmt3b, increased carcinogen-induced squamous tumors in murine epidermis, with combined deletion leading to more aggressive and metastatic carcinomas. Our plain-language summary of this paper — not a Tressless recommendation.
The study explored the role of Dnmt3a and Dnmt3b in skin carcinogenesis, revealing that their loss did not impact epidermal homeostasis but promoted squamous transformation via PPAR-γ. Loss of Dnmt3a in keratinocytes increased tumorigenesis post-DMBA treatment, with Dnmt3a-cKO mice developing more tumors with high PPAR-γ expression, suggesting PPAR-γ inhibition as a potential therapy. The study noted a slight increase in mutations, particularly Cytosine to Thymine, in Dnmt3a-cKO tumors, possibly due to impaired TDG glycosylase activity. It concluded that Dnmt3a affects tumor initiation rather than progression, as more tumors were initiated without increased H-RAS or N-RAS mutations. Despite these findings, Dnmt3a and Dnmt3b were not crucial for epidermal differentiation or homeostasis, indicating the complexity of DNA methylation in gene regulation and tumorigenesis, warranting further research.
