Overexpression of VIRMA confers vulnerability to breast cancers via the m⁶A-dependent regulation of unfolded protein response.

ABSTRACT: Virilizer-like m⁶A methyltransferase-associated protein (VIRMA) maintains the stability of the m⁶A writer complex. Although VIRMA is critical for RNA m⁶A deposition, the impact of aberrant VIRMA expression in human diseases remains unclear. We show that VIRMA is amplified and overexpressed in 15-20% of breast cancers. Of the two known VIRMA isoforms, the nuclear-enriched full-length but not the cytoplasmic-localised N-terminal VIRMA promotes m⁶A-dependent breast tumourigenesis in vitro and in vivo. Mechanistically, we reveal that VIRMA overexpression upregulates the m⁶A-modified long non-coding RNA, NEAT1, which contributes to breast cancer cell growth. We also show that VIRMA overexpression enriches m⁶A on transcripts that

SUBMITTER: Lee Q 

PROVIDER: S-EPMC10198946 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature