滨州医学院学报2025，Vol.48Issue(3)：237-242,283,7.DOI:10.19739/j.cnki.issn1001-9510.2025.03.003
p53突变型结直肠癌中AGAP2的相关研究
Study on AGAP2 in p53-mutant colorectal cancer
摘要
Abstract
Objective To investigate the expression differences of AGAP2(with GTPase domain,Anchor protein repeats and ArfGAP of PH domain 2),GRIA2(glutamate ionotropic receptor AMPA type subunit 2),GRIP1(glutamate receptor interacting protein 1),and MCC regulator of WNT signaling pathway in wild-type and mutant p53 colorectal cancer,and to assess their im-pact on cellular biological behavior,particularly focusing on the mechanism of AGAP2 in p53 mutant colorectal cancer.Methods Samples of p53 wild-type and mutant colorectal cancer and adjacent tissues were collected,and the expressions of AGAP2,GRIA2,GRIP1 and MCC were detected by qRT-PCR and Western blot.The interaction between AGAP2 and GRIA2,GRIP1 and MCC was analyzed by bioinformatics,and verified by immunoprecipitation technology.After AGAP2 was knocked out in p53 mutant colorectal cancer cell lines HT29 and SW480,CCK-8 was used to detect cell proliferation,Transwell was used to detect invasion ability,and glutathione(GSH),GPX(glutathione peroxidase)activity,free radicals and Fe2+were used to detect fer-roptosis.Results Compared with the adjacent tissues,the mRNA and protein expression levels of AGAP2,GRIA2 and GRIP1 in p53 wild-type and mutant colorectal cancer tissues were significantly up-regulated,while MCC expression was significantly down-regulated.Bioinformatics analysis showed that AGAP2 interacted with GRIA2,GRIP1 and MCC,which was verified by im-munoprecipitation experiment.After AGAP2 was knocked out in p53 mutant colorectal cancer cell lines HT-29 and SW480,the proliferation of CCK-8 cells was significantly reduced,and the invasion ability of Transwell cells was inhibited.The detection of ferroptosis index showed that GSH,GPX activity and GPX4 protein levels were all down-regulated,while the free radical level and Fe2+concentration were significantly up-regulated.Conclusion The high expression of AGAP2 in p53 mutant colorectal cancer may promote malignant behavior of cancer cells by regulating GRIA2,GRIP1,and MCC.关键词
p53突变型结直肠癌/AGAP2Key words
p53 mutant colorectal cancer/AGAP2分类
医药卫生引用本文复制引用
李甲宁,郭松,张天泽,曹连盟,李河圣..p53突变型结直肠癌中AGAP2的相关研究[J].滨州医学院学报,2025,48(3):237-242,283,7.基金项目
山东省医药卫生科技发展计划(2016WS0020) （2016WS0020）
