Stabilization of RRBP1 mRNA via an m⁶A-dependent manner in prostate cancer constitutes a therapeutic vulnerability amenable to small-peptide inhibition of METTL3.

ABSTRACT: Mounting evidence has implicated the RNA m⁶A methylation catalyzed by METTL3 in a wide range of physiological and pathological processes, including tumorigenesis. The detailed m⁶A landscape and molecular mechanism of METTL3 in prostate cancer (PCa) remains ill-defined. We find that METTL3 is overexpressed in PCa and correlates with worse patient survival. Functional studies establish METTL3 as an oncoprotein dependent on its m⁶A enzymatic activity in both AR⁺ and AR^- PCa cells. To dissect the regulatory network of m⁶A pathway in PCa, we map the m⁶A landscape in clinical tumor samples using m⁶A-seq and identify genome-wide METTL3-binding transcripts via RIP-seq. Mechanistically, we discover RRBP1 as a di

SUBMITTER: Feng Y 

PROVIDER: S-EPMC11455910 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature