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·1220 · 南 京 医 科 大 学 学 报 2025年9月

lactylation was significantly upregulated in clinical OC samples，with PARP1 lactylation at K192 being one of the most common
modifications. The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1 ⁃ WT but not mutant
PARP1. Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal⁃regulated kinases 1/2（ERK1/
2）. Conclusion：This study uncovered a novel PTM of PARP1 in OC，lactylation，and demonstrated that lactylation at K192 is crucial
in regulating OC cell growth and migration via the ERK1/2 pathway. Further investigations are required to elucidate the broader
functional implications of PARP1 lactylation and its therapeutic potential.
［Key words］ PARP1；lactylation；migration；proliferation；ovarian cancer cells
［J Nanjing Med Univ，2025，45（09）：1219⁃1228，1241］

［11］ ［12］
Ovarian cancer（OC）ranks the third most common cells like macrophages ，and plants . Like other
cancer among women and the leading cause of cancer⁃ PTMs，such as acetylation，methylation，phosphoryla⁃
related mortality in gynecological cancers，with over tion，and ubiquitination，lactylation has been identified
［8］
22 000 women diagnosed and approximately 14 000 as another epigenetic modulator of gene expression .
［1］
dying from OC annually in the United States . Early Poly（ADP ⁃ ribose）polymerase ⁃ 1（PARP1）is a
diagnosis of OC is challenging，primarily due to its subtle PTM enzyme that catalyzes the removal of ADP⁃ribose
initial symptoms，such as bloating，indigestion，lower residues from oxidized nicotinamide adenine dinucleo⁃
+
back pain，and frequent urination，which are often mis⁃ tide（NAD ）to the target substrate，forming poly（ADP⁃
［2］
taken for other benign conditions . leading to diagnos⁃ ribose）（PAR）. This process is essential for various cel⁃
tic delays. As a result，over 70% of OC cases are diag⁃ lular functions，including the repair of double ⁃ strand
nosed at an advanced stage. Late diagnosis often leaves breaks，cell adhesion and movement，transcriptional
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patients with limited treatment options and a poor prog⁃ regulation，innate immunity，and apoptosis . Nu⁃
［3］
nosis . While OC has several subtypes，its treatment merous studies have shown that PARP1 levels are up⁃
［15-16］
remains relatively consistent，primarily involving tumor regulated in diverse tumors . The crosstalk between
debulking surgery and platinum ⁃ based combination acetylation，ubiquitination，and SUMOylation at multi⁃
［4］
chemotherapy with taxanes . Although OC is consid⁃ ple PARP1 sites has been implicated in the pathogene⁃
ered as a platinum⁃sensitive tumor with a high response sis of neurodegenerative diseases ［17］ . Moreover，PARP1
rate to first ⁃ line standard treatment，75% of patients acetylation has been shown to promote nuclear factor
with advanced OC will still experience metastasis，recur⁃ kappa B（NF⁃κB）⁃mediated chemoresistance to plati⁃
［18］
rence，and ultimately resistance，resulting in poor long⁃ num compounds in cancer cells . However，studies
term survival. Discovering new biomarkers associated on the lactylation of PARP1 remain scarce.
with OC is crucial for improving treatment outcomes for In this study，we found that lactylation was the
patients with this disease. most significantly upregulated PTM in OC samples.
Post⁃translational modifications（PTMs），which in⁃ Using label ⁃ free mass spectrometry，we identified 10
volve the covalent modification of amino acids within upregulated and 16 downregulated lactylation sites
proteins，have been shown to play crucial roles in nu⁃ within proteins that are important in multiple key cellu⁃
［5-7］
merous cellular processes . Advances in high⁃through⁃ lar processes. We also demonstrated that lactylation of
put sequencing technologies have led to the discovery PARP1 at the K192 site significantly inhibits the growth
of novel PTMs，including lactylation. In 2019，Zhang et and migration of OC cells by downregulating phosphor⁃
［8］
al first reported histone lactylation，which involves ylated（p）⁃extracellular signal⁃regulated kinases（ERKs）.
the addition of a lactyl group to lysine residues on his⁃
1 Materials and methods
tone tails. Since then，histone lactylation has been in⁃
creasingly reported in various diseases，cell types，and 1.1 Materials
organisms，including cancers such as non ⁃ small cell 1.1.1 Cell lines and cell culture
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lung cancer and bladder cancer ，immune⁃related The human OC cell line，A2780 was obtained