Regulation of Histone Emulsification by HPDL via LDHA/LDHB Promotes EC Cell Proliferation

Area of Science:

• Oncology
• Epigenetics
• Metabolic pathways

Background:

• The role of 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) in endometrial cancer (EC) progression is unclear.
• Its involvement in metabolic-epigenetic crosstalk, specifically lactate-driven histone lactylation, needs investigation.

Purpose of the Study:

• To investigate the mechanistic contribution of HPDL to endometrial cancer pathogenesis.
• To explore the link between HPDL, lactate metabolism, and histone lactylation in EC.

Main Methods:

• Generated stable HPDL-overexpressing and knockdown EC cell lines.
• Conducted functional assays, xenograft models, and molecular analyses including lactate, lactylation, and ChIP assays.
• Utilized sodium oxamate as a lactate modulator and assessed LDHA/LDHB knockdown effects.

Main Results:

• HPDL modulation affected intracellular lactate and histone lactylation (H3K18la) levels.
• HPDL overexpression enhanced EC cell proliferation, migration, and invasion in vitro and accelerated tumor growth in vivo.
• H3K18la occupancy at LDHA/LDHB promoters was linked to HPDL expression levels.

Conclusions:

• HPDL regulates histone lactylation through LDHA/LDHB.
• HPDL promotes endometrial cancer cell proliferation, migration, and invasion.