Yan Wang1,#, Jialei Zhu2,#, Shiyang Wei3,4,#, Lijie Jin1, Zhanqiu Liu1, Jie Xu1, Nana Yang1, Xuefeng Jiang4, Caizhi Wang1,*, Lingling Wang1,*
Oncology Research, Vol.34, No.5, 2026, DOI:10.32604/or.2026.068833
- 22 April 2026
Abstract Background: The role of 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) in endometrial cancer (EC) progression remains poorly understood, particularly its involvement in metabolic-epigenetic crosstalk via lactate-driven histone lactylation. This study aimed to investigate HPDL’s mechanistic contribution to EC pathogenesis. Methods: Stable HPDL-overexpressing and knockdown EC cell lines (HEC-1-B and AN3CA) were generated using lentiviral vectors. Functional assays (proliferation, migration, invasion), subcutaneous xenograft models in BALB/c nude mice, and molecular analyses were conducted. Lactate levels, Pan-lysine lactylation (pan-kla), histone H3K18 lactylation (H3K18la), and effects of sodium oxamate (lactate modulator) were assessed. Lactate Dehydrogenase A/Lactate Dehydrogenase B (LDHA/LDHB) knockdown,… More >