河北医学2026，Vol.32Issue(5)：705-713,9.DOI:10.3969/j.issn.1006-6233.2026.05.01
METTL3通过m6A调控GBAP1经PI3K/AKT通路促膀胱癌进展的影响
METTL3 Promotes Bladder Cancer Progression via m6A-Modified LncRNA GBAP1 Through PI3K/AKT Pathway
摘要
Abstract
Objective:To reveal the molecular mechanism by which METTL3 regulates LncRNA GBAP1 expression through m6A modification,thereby activating the PI3K/AKT pathway and promoting bladder cancer progression.Methods:qRT-PCR was used to detect the expression levels of METTL3 and GBAP1 in the nor-mal human uroepithelial cell line SV-HUC-1 and bladder cancer cell lines(T24,UM-UC-3,J82,and 5637).T24 cells were divided into nine groups:pcDNA NC,pcDNA METTL3,sh-NC,sh-METTL3,sh-METTL3+oe-NC,sh-METTL3+oe-GBAP1,si-NC,si-GBAP1,and si-GBAP1+740Y-P.Methylated RNA immunoprecipitation(MeRIP)and RNA immunoprecipitation(RIP)assays were performed to assess METTL3-mediated m6A modification levels of GBAP1.Colony formation,Transwell,and wound healing as-says were used to evaluate cell invasion and migration.Intracellular Cu+levels were measured.Western blot-ting was performed to detect the expression of cuproptosis-related proteins and PI3K/AKT pathway compo-nents.A nude mouse xenograft model was used to assess tumor volume and weight.Results:Compared with SV-HUC-1 cells,both METTL3 and GBAP1 were significantly upregulated in bladder cancer cell lines(T24,UM-UC-3,J82,and 5637)(P<0.05),with the most pronounced differences observed in T24 cells.MeRIP and RIP assays showed that METTL3 antibody significantly enriched the m6A methylation level of GBAP1 and increased GBAP1 expression(P<0.05).Compared with the sh-NC group,the sh-METTL3 group showed significantly reduced GBAP1 expression,colony number,invading cell number,cell migration rate,p-PI3K/PI3K and p-AKT/AKT ratios,as well as xenograft tumor volume and weight(P<0.05),while Cu+levels and the protein levels of FDX1,LIAS,LIPT1,and DLAT were significantly increased(P<0.05).Compared with the sh-METTL3+oe-NC group,the sh-METTL3+oe-GBAP1 group exhibited significantly in-creased GBAP1 expression,colony number,invading cell number,cell migration rate,p-PI3K/PI3K and p-AKT/AKT ratios,and xenograft tumor volume and weight(P<0.05),along with decreased Cu+levels and FDX1,LIAS,LIPT1,and DLAT protein levels(P<0.05).Compared with the si-NC group,the si-GBAP1 group had significantly lower p-PI3K/PI3K and p-AKT/AKT ratios,colony number,invading cell number,and cell migration rate(P<0.05),while Cu+levels and FDX1,LIAS,LIPT1,and DLAT protein levels were significantly higher(P<0.05).Compared with the si-GBAP1 group,the si-GBAP1+740Y-P group showed significantly increased p-PI3K/PI3K and p-AKT/AKT ratios,colony number,invading cell number,and cell migration rate(P<0.05),and decreased Cu+levels and FDX1,LIAS,LIPT1,and DLAT protein levels(P<0.05).Conclusion:METTL3 and GBAP1 are significantly upregulated in bladder cancer cells.MET-TL3 regulates LncRNA GBAP1 expression via m6A methylation,thereby inhibiting cuproptosis and promoting malignant progression of bladder cancer through the PI3K/AKT pathway.关键词
膀胱癌/METTL3/LncRNA GBAP1/m6A/铜死亡Key words
Bladder cancer/METTL3/LncRNA GBAP1/m6A/Cuproptosis引用本文复制引用
吴文婧,李淑洁,徐加佳,关文芳,尹倩雯,孙晓敏,陈葳..METTL3通过m6A调控GBAP1经PI3K/AKT通路促膀胱癌进展的影响[J].河北医学,2026,32(5):705-713,9.基金项目
陕西省自然科学基金(编号:2023-JC-YB-666) （编号:2023-JC-YB-666）
