@Article{or.2026.068833,
AUTHOR = {Yan Wang, Jialei Zhu, Shiyang Wei, Lijie Jin, Zhanqiu Liu, Jie Xu, Nana Yang, Xuefeng Jiang, Caizhi Wang, Lingling Wang},
TITLE = {Regulation of Histone Emulsification by HPDL via LDHA/LDHB Promotes EC Cell Proliferation},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {5},
PAGES = {--},
URL = {http://www.techscience.com/or/v34n5/67042},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> 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. <b>Methods:</b> 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, promoter activity assays, and chromatin immunoprecipitation (ChIP) were performed to evaluate H3K18la occupancy at LDHA/LDHB promoters. <b>Results:</b> HPDL knockdown reduced intracellular lactate, Pan-Kla, and H3K18la levels, while overexpression elevated these markers. Sodium oxamate amplified lactate and lactylation in HPDL-overexpressing cells but suppressed histone lactylation independently of HPDL. LDHA/LDHB knockdown diminished lactylation, repressed HPDL expression, and inhibited promoter activity. ChIP revealed H3K18la enrichment at LDHA/LDHB promoters in HPDL-overexpressing cells and reduced occupancy in knockdown models. HPDL enhanced EC cell proliferation, migration, and invasion <i>in vitro</i>. <i>In vivo</i>, HPDL-overexpressing xenografts exhibited accelerated tumor growth and larger volumes compared to controls. <b>Conclusions:</b> HPDL regulates histone lactylation via LDHA/LDHB and promotes the proliferation of EC cells.},
DOI = {10.32604/or.2026.068833}
}