Autophagy of the m⁶A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis.

ABSTRACT: Here we show that FTO as an N⁶-methyladenosine (m⁶A) RNA demethylase is degraded by selective autophagy, which is impaired by low-level arsenic exposure to promote tumorigenesis. We found that in arsenic-associated human skin lesions, FTO is upregulated, while m⁶A RNA methylation is downregulated. In keratinocytes, chronic relevant low-level arsenic exposure upregulated FTO, downregulated m⁶A RNA methylation, and induced malignant transformation and tumorigenesis. FTO deletion inhibited arsenic-induced tumorigenesis. Moreover, in mice, epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. Targeting FTO genetically or pharmacologically inhibits the tumorigenicity of arsenic-transformed tumor cells. We

SUBMITTER: Cui YH 

PROVIDER: S-EPMC8041927 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature