南京医科大学学报（自然科学版）2025，Vol.45Issue(9)：1219-1228,1241,11.DOI:10.7655/NYDXBNSN241251
PARP1在K192位点的乳酸化抑制卵巢癌细胞的迁移和增殖
Lactylation of PARP1 at K192 inhibits the migration and proliferation of ovarian cancer cells
摘要
Abstract
Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-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.关键词
PARP1/乳酸化/迁移/增殖/卵巢癌细胞Key words
PARP1/lactylation/migration/proliferation/ovarian cancer cells分类
医药卫生引用本文复制引用
苏宁,应小燕,曹颖,张淑平,吴少君,孙鸿展,唐雪俊,袁冬兰,张东,杨莉莉..PARP1在K192位点的乳酸化抑制卵巢癌细胞的迁移和增殖[J].南京医科大学学报（自然科学版）,2025,45(9):1219-1228,1241,11.基金项目
国家自然科学基金(32070840,32370912) （32070840,32370912）
江苏省妇幼健康重点学科基金(FXK201712) （FXK201712）
