%0 Journal Article
%A Zuidhof, Hidde R
%A Müller, Christine
%A Kortman, Gertrud
%A Wardenaar, René
%A Stepanova, Ekaterina
%A Loayza-Puch, Fabricio
%A Calkhoven, Cornelis F
%T The m6A demethylase FTO promotes C/EBPβ-LIP translation to perform oncogenic functions in breast cancer cells.
%J The FEBS journal
%V 292
%N 10
%@ 0014-2956
%C Oxford [u.a.]
%I Wiley-Blackwell
%M DKFZ-2025-00462
%P 2688-2709
%D 2025
%Z 2025 May;292(10):2688-2709
%X N6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are regulated through yet unidentified mechanisms. Differential translation of CEBPB mRNA into the C/EBPβ transcription factor isoform C/EBPβ-LIP is known to act in a pro-oncogenic manner in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBPβ-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBPβ-LIP.
%K C/EBPβ (Other)
%K FTO (Other)
%K breast cancer (Other)
%K mRNA translation (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40022434
%R DOI:10.1111/febs.70033
%U https://inrepo02.dkfz.de/record/299504