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000299504 1001_ $$aZuidhof, Hidde R$$b0
000299504 245__ $$aThe m6A demethylase FTO promotes C/EBPβ-LIP translation to perform oncogenic functions in breast cancer cells.
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000299504 500__ $$a2025 May;292(10):2688-2709
000299504 520__ $$aN6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are regulated through yet unidentified mechanisms. Differential translation of CEBPB mRNA into the C/EBPβ transcription factor isoform C/EBPβ-LIP is known to act in a pro-oncogenic manner in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBPβ-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBPβ-LIP.
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000299504 650_7 $$2Other$$aC/EBPβ
000299504 650_7 $$2Other$$aFTO
000299504 650_7 $$2Other$$abreast cancer
000299504 650_7 $$2Other$$amRNA translation
000299504 7001_ $$aMüller, Christine$$b1
000299504 7001_ $$aKortman, Gertrud$$b2
000299504 7001_ $$aWardenaar, René$$b3
000299504 7001_ $$0P:(DE-He78)dc4f734225935c3650fde7619c82ed92$$aStepanova, Ekaterina$$b4
000299504 7001_ $$0P:(DE-He78)4af0380446b05b5f1995502016151a1b$$aLoayza-Puch, Fabricio$$b5$$udkfz
000299504 7001_ $$00000-0001-6318-7210$$aCalkhoven, Cornelis F$$b6
000299504 773__ $$0PERI:(DE-600)2172518-4$$aDOI:10.1111/febs.70033$$n10$$p2688-2709$$tThe FEBS journal$$v292$$x0014-2956$$y2025
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