Histone Lactylation Promotes Proliferation and Migration of TNBC Cells via Upregulating MCM7 Transcription.

Elevated histone lactylation is crucial in the initiation and progression of various cancers. Although its role in breast cancer remains unconfirmed, the increased lactate release from enhanced glycolysis in triple-negative breast cancer (TNBC) suggests a potential link. In order to investigate the effect of histone lactylation on TNBC, we detected the lactate production and histone lactylation levels. Chromatin immunoprecipitation (ChIP) assay was used to confirm that minichromosome maintenance complex component (MCM) 7 is a downstream target. A variety of experimental techniques including, cell viability, colony formation assay, apoptosis assay, and transwell assay were used to describe the cell proliferation and migration ability. Histone lactylation levels were increased in TNBC tissues. Inhibiting lactate production suppressed the proliferation and migration of TNBC cells and histone lactylation in TNBC cells. Histone lactylation modulated MCM7 expression and translation, and MCM7 participated in histone lactylation regulation of TNBC cell function. These data show that enhanced glycolysis in TNBC cells results in increased lactate production, directly contributing to histone lactylation and subsequent activation of MCM7 promoter. Our results highlight that targeting the feedback loop involving glycolysis, lactate production, histone lactylation, and MCM7 transcription could be a therapeutic strategy for TNBC by inhibiting cell proliferation and migration.