中国医药科学2025，Vol.15Issue(19)：28-32,70,6.DOI:10.20116/j.issn2095-0616.2025.19.06
c-IAP2通过降解丙酮酸脱氢酶促进Warburg效应和骨肉瘤恶性进展的机制研究
Mechanism of c-IAP2 promotes Warburg effect and malignant progression of osteosarcoma by degrading pyruvate dehydrogenase
摘要
Abstract
Objective This study aims to explore the role of cell apoptosis inhibition protein-2(c-IAP2)in osteosarcoma,particularly how it promotes the Warburg effect and malignant progression by degrading pyruvate dehydrogenase(PDH).Methods Experiments were conducted using the U-2OS cell line.Quantitative real-time PCR(qPCR)was used to detect mRNA levels of c-IAP2,PDHA,and PDHB.Co-immunoprecipitation(Co-IP)and Western blot(WB)were used to analyze interactions between c-IAP2 and PDHA/PDHB proteins.Cell viability,scratch,and invasion assays assessed c-IAP2's effects on proliferation,migration,and invasion.Glucose,lactate,PDH content,oxygen consumption rate(OCR),and extracellular acidification rate(ECAR)assays evaluated aerobic glycolysis levels.Results In the qPCR experiment,the overexpressed group exhibited elevated c-IAP2 mRNA expression levels(P<0.05),while PDHA(P<0.05)and PDHB(P>0.05)expression decreased.The knockdown group showed reduced c-IAP2 mRNA expression levels(P<0.01).In the Co-IP experiment,an interaction was observed between c-IAP2 and PDHA/PDHB.In the WB experiment,c-IAP2 overexpression promoted PDH degradation.In cell viability assays,invasion assays,and scratch assays,the overexpressed group exhibited significantly higher cell proliferation capacity(P<0.01),invasion capacity(P<0.05),and migration capacity(P<0.01)compared to the control group.The overexpressed group exhibited higher cellular lactate production(P<0.05),OCR(P<0.01),and ECAR(P<0.01)compared to the control group.Additionally,the glucose content(P<0.05)and PDH content(P<0.05)in the overexpressed group were lower than those in the control group.Conclusion c-IAP2 overexpression promotes the Warburg effect and enhances osteosarcoma proliferation,migration,and invasion by degrading PDH.关键词
c-IAP2/骨肉瘤/丙酮酸脱氢酶/Warburg效应/恶性进展Key words
C-IAP2/Osteosarcoma/Pyruvate dehydrogenase/Warburg effect/Malignant progression分类
医药卫生引用本文复制引用
陈宝林,温杰..c-IAP2通过降解丙酮酸脱氢酶促进Warburg效应和骨肉瘤恶性进展的机制研究[J].中国医药科学,2025,15(19):28-32,70,6.基金项目
内蒙古医科大学联合项目(YKD2022LH037) （YKD2022LH037）
内蒙古医学科学院公立医院科研联合基金项目(2024GLLH0495). （2024GLLH0495）
