Bisphenol A Promotes Ovarian Cancer Proliferation and Migration through the HK2/H3K18la/IGF2BP3 Sequential Regulatory Axis

Bisphenol A (BPA), an endocrine-disrupting chemical with estrogenic activity, has been implicated in Cancer development, although its role remains controversial. This study investigated the effects of BPA on ovarian Cancer and its underlying mechanisms. BPA treatment dose-dependently (0-10 μM) increased cell viability and invasion. Kyoto Encyclopedia of Genes and Genomes analysis revealed the enrichment of the central carbon metabolism pathway following BPA exposure. Consistent with this, BPA upregulated glycolytic Enzymes HK2 and LDHA. In addition, BPA activated ERα, which enhanced HK2 transcription and promoted glycolysis. The resulting lactate accumulation increased histone H3 lysine 18 lactylation (H3K18la), enriched at the IGF2BP3 promoter, to upregulate its expression. IGF2BP3 then stabilized HK2 mRNA via m6A recognition, amplifying the glycolysis. Our findings suggest that BPA promotes ovarian Cancer progression through the HK2/H3K18la/IGF2BP3 sequential regulatory axis, providing insights for epigenetic-targeted therapies.

H3K18 lactylation; IGF2BP3; bisphenol A; glycolysis; ovarian cancer.