中国肿瘤生物治疗杂志2026,Vol.33Issue(8):886-898,13.DOI:10.3872/j.issn.1007-385X.2026.08.009
PADI1促进肾透明细胞癌细胞增殖、迁移和侵袭及其可能的机制
PADI1 promotes proliferation,migration,and invasion of clear cell renal cell carcinoma cells and its possible underlying mechanism
摘要
Abstract
Objective:This study aimed to investigate the impact of peptidylarginine deiminase 1(PADI1)on the migration,proliferation,and invasion of clear cell renal cell carcinoma(ccRCC)cells and the related molecular mechanisms.Methods:Differentially expressed genes between ccRCC and adjacent normal tissues were screened using transcriptome sequencing,and their expression levels were analyzed via GEPIA,TIMER2.0,and other bioinformatics platforms.A total of 59 ccRCC specimens were obtained from patients who underwent nephrectomy at the Department of Urology,The Fourth Hospital of Hebei Medical University between 2024 and 2025.The expression levels of PADI1 in cancerous and adjacent tissues were measured by RT-qPCR and immunohistochemistry(SP method),and their correlations with various clinicopathological parameters were analyzed.The effects of PADI1 on migration,proliferation,and invasion of ccRCC cells were evaluated by wound-healing,CCK-8,colony formation,and Transwell assays.Flow cytometry was used to examine the effects of PADI1 on cell cycle,and Western blotting was employed to detect changes in the expression levels of proteins related to the cornified envelope(CE)formation pathway and epithelial-mesenchymal transition(EMT)in the transfected A498 cells.Results:The relative expression level of PADI1 in ccRCC tissues was significantly higher than that in adjacent normal tissues(P<0.01),and was correlated with patient age,lymph node metastasis,distant metastasis,and clinical stage(P<0.05).Transfection of A498 and ACHN cells with si-PADI1 effectively down-regulated PADI1 mRNA and protein expression(P<0.05),whereas transfection with overexpression plasmid significantly up-regulated its expression(P<0.05).Knockdown of PADI1 significantly inhibited cell migration(P<0.05),proliferation(P<0.05),and invasion(P<0.001),while PADI1 overexpression enhanced these abilities(P<0.05,P<0.05,and P<0.001),whereas no significant effect on cell cycle progression was detected.Western blotting results showed that altered PADI1 expression in A498 cells was accompanied by changes in the expression levels of proteins related to EMT and the CE formation pathway.Conclusion:PADI1 is highly expressed in ccRCC and associated with patient age,lymph node metastasis,distant metastasis,and clinical stage.Elevated PADI1 expression affects the CE formation pathway and accelerates EMT progression,thereby enhancing the migration,proliferation,and invasion of renal cancer cells.关键词
肽基精氨酸脱亚胺酶1/肾透明细胞癌/上皮-间充质转化/角质化包膜/细胞增殖/细胞侵袭Key words
peptidylarginine deiminase 1(PADI1)/clear cell renal cell carcinoma(ccRCC)/epithelial-mesenchymal transition(EMT)/cornified envelope(CE)/cell proliferation/cell invasion分类
医药卫生引用本文复制引用
李涛,牛云峰,王杏丹,曾琨鹏,陈浩,胡文实,樊博..PADI1促进肾透明细胞癌细胞增殖、迁移和侵袭及其可能的机制[J].中国肿瘤生物治疗杂志,2026,33(8):886-898,13.基金项目
河北省财政厅政府资助临床医学优秀人才项目(ZF2026205) (ZF2026205)