METTL3-mediated N⁶-methyladenosine modification of STAT5A promotes gastric cancer progression by regulating KLF4.

ABSTRACT: N⁶-methyladenosine (m⁶A) is the predominant post-transcriptional RNA modification in eukaryotes and plays a pivotal regulatory role in various aspects of RNA fate determination, such as mRNA stability, alternative splicing, and translation. Dysregulation of the critical m⁶A methyltransferase METTL3 is implicated in tumorigenesis and development. Here, this work showed that METTL3 is upregulated in gastric cancer tissues and is associated with poor prognosis. METTL3 methylates the A2318 site within the coding sequence (CDS) region of STAT5A. IGF2BP2 recognizes and binds METTL3-mediated m⁶A modification of STAT5A through its GXXG motif in the KH3 and KH4 domains, leading to increased stability of STAT5A mRNA. In addition, both METTL3 and IGF2BP2 ar

SUBMITTER: Zang Y 

PROVIDER: S-EPMC11271408 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature