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In HCC, this regulatory axis is disrupted whereby &lt;i&gt;FOXM1&lt;\/i&gt; overrides DNMT1-mediated methylation, upregulating TACC3, and decoupling &lt;i&gt;TACC3&lt;\/i&gt; from the KAT2A-associated NOTCH4 co-expression module. This rewiring is licensing tumor-specific cell-cycle progression and epigenetic plasticity. Thus, &lt;i&gt;FOXM1&lt;\/i&gt; reshapes the TACC3-KAT2A interaction, while DNMT1 drives context-dependent DNA methylation, activating the CDK1-inhibitory kinase PKMYT1.Conclusions: We uncovered TACC3-KAT2A as an emerging regulatory axis caused by alternative splicing in HCC and propose FOXM1-driven TACC3 inhibition to synergistically disrupt mitotic fidelity and transcriptional regulation, potentially offering new therapeutic avenues for HCC with reduced toxicity to the normal liver.<\/jats:p>","DOI":"10.3350\/cmh.2025.1370","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T23:46:37Z","timestamp":1769557597000},"page":"808-828","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FOXM1 influences DNA methylation to augment TACC3 alternative splicing directed by KAT2A in hepatocellular carcinoma"],"prefix":"10.3350","volume":"32","author":[{"given":"Li 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