084 mRNA methylation in skin tumorigenesis and therapeutic resistance

نویسندگان

چکیده

Analogous to DNA and histone modifications, RNA molecules are chemically modified, the study of which gives rise field called epitranscriptomics. Among these N6-methyladenosine (m6A) methylation is most abundant internal modification in messenger (mRNA) non-coding eukaryotic cells, regulates metabolism, including decay, translation nuclear processing. However, regulatory functional role m6A skin cancer remain poorly understood. Recently we demonstrated that mRNA demethylase FTO promotes tumorigenesis resistance immunotherapy melanoma. In addition, using skin-specific conditional knockout mouse models, combination with vitro cellular recently have a pivotal development. as an degraded by selective autophagy, impaired low-level arsenic exposure promote tumorigenesis. We found arsenic-associated human lesions, up-regulated, while down-regulated. keratinocytes, chronic relevant up-regulated FTO, down-regulated methylation, induced malignant transformation Moreover, mice, epidermis-specific deletion prevented UVB irradiation. Targeting genetically or pharmacologically inhibits tumorigenicity arsenic-transformed tumor cells. identified NEDD4L m6A-modified gene target FTO. Finally, stabilizes protein through inhibiting p62-mediated autophagy. Our reveals FTO-mediated dysregulation epitranscriptomic mechanism may open up new opportunities reduce burden.

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2022

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2022.05.019