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The modification is mediated by multicomponent methyltransferase complexes (so\u2010called writers) and is reversed through the action of the m6A\u2010demethylases fat mass and obesity\u2010associated (FTO) and alkB homolog 5 (ALKBH5) (so\u2010called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple\u2010negative breast cancer (TNBC). However, little is known about genome\u2010wide or specific downstream regulation by FTO. Here, we examined changes in the genome\u2010wide 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\u2010mesenchymal transition (EMT) are regulated through yet unidentified mechanisms. Differential translation of CEBPB mRNA into the C\/EBP\u03b2 transcription factor isoform C\/EBP\u03b2\u2010LIP is known to act in a pro\u2010oncogenic manner in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C\/EBP\u03b2\u2010LIP expression, suggesting that FTO has oncogenic functions through regulation of C\/EBP\u03b2\u2010LIP.<\/jats:p>","DOI":"10.1111\/febs.70033","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:26:38Z","timestamp":1741742798000},"page":"2688-2709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The\n                    <scp>m6A<\/scp>\n                    demethylase\n                    <scp>FTO<\/scp>\n                    promotes C\/\n                    <scp>EBP\u03b2<\/scp>\n                    \u2010\n                    <scp>LIP<\/scp>\n                    translation to perform oncogenic functions in breast cancer cells"],"prefix":"10.1111","volume":"292","author":[{"given":"Hidde R.","family":"Zuidhof","sequence":"first","affiliation":[{"name":"European Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen, University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"European Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen, University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrud","family":"Kortman","sequence":"additional","affiliation":[{"name":"European Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen, University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Wardenaar","sequence":"additional","affiliation":[{"name":"European Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen, University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Stepanova","sequence":"additional","affiliation":[{"name":"Translational Control and Metabolism German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabricio","family":"Loayza\u2010Puch","sequence":"additional","affiliation":[{"name":"Translational Control and Metabolism German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-7210","authenticated-orcid":false,"given":"Cornelis F.","family":"Calkhoven","sequence":"additional","affiliation":[{"name":"European Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen, University of Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"31","volume-title":"Post\u2010Transcriptional Gene Regulation by mRNA Modifications","author":"Zhao B. 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