{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:36:59Z","timestamp":1786117019483,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Lysine \u03b2-hydroxybutyrylation (Kbhb) is a metabolite-derived post-translational modification of histone and non-histone proteins that couples \u03b2-hydroxybutyrate (BHB) availability to gene expression. Yet the transcription factors that govern the Kbhb substrate program in cancer remain unidentified. Existing studies have cataloged Kbhb-modified substrates or examined individual proteins, without identifying the transcriptional regulators of the program in a defined tumor context. Here, we performed network-based master regulator analysis (MRA), implemented in the viper package, on a molecular signature restricted to experimentally validated Kbhb substrates, across two independent PAM50 Basal-like breast cancer (BLBC) cohorts profiled on orthogonal platforms: TCGA-BRCA (RNA-seq; n = 195 tumor, 113 normal) and METABRIC (microarray; n = 209 tumor, 148 normal). Dataset-specific regulatory networks were inferred with ARACNe-AP and integrated by cross-platform Stouffer meta-analysis. Of 1493 Kbhb substrates, 1322 and 1213 were expressed in the respective cohorts. The analysis identified seven concordant transcriptional master regulators (six activated, one repressed; cross-cohort NES correlation r = 0.64), with CENPA (meta-NES +4.55) and FOXM1 (meta-NES +4.27) as the dominant drivers. These findings nominate a BHB\u2013Kbhb\u2013FOXM1\/CENPA axis linking ketone-body metabolism to mitotic transcription, with potentially protumoral implications for ketogenic regimens in BLBC.<\/jats:p>","DOI":"10.3390\/ijms27157059","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:03:27Z","timestamp":1786021407000},"page":"7059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A \u03b2-Hydroxybutyrylation\u2013FOXM1\/CENPA Axis Links Ketone-Body Metabolism to Mitotic Transcription in Basal-like Breast Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-6133","authenticated-orcid":false,"given":"Hugo","family":"Tovar","sequence":"first","affiliation":[{"name":"Computational Genomics Division, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-1397","authenticated-orcid":false,"given":"Enrique","family":"Hern\u00e1ndez-Lemus","sequence":"additional","affiliation":[{"name":"Computational Genomics Division, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Urz\u00ec, A.G., Tropea, E., Gattuso, G., Spoto, G., Marsala, G., Calina, D., Libra, M., and Falzone, L. 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