目的探究蛋白质二硫键异构酶A3(protein disulfide isomerase A3,PDIA3)在子宫内膜癌(endometrial cancer,EC)组织中的表达水平、临床意义及其对Ishikawa细胞的影响。方法利用TCGA数据库分析不同内膜组织中PDIA3的表达水平差异,探究其...目的探究蛋白质二硫键异构酶A3(protein disulfide isomerase A3,PDIA3)在子宫内膜癌(endometrial cancer,EC)组织中的表达水平、临床意义及其对Ishikawa细胞的影响。方法利用TCGA数据库分析不同内膜组织中PDIA3的表达水平差异,探究其与EC患者临床病理参数及预后间的联系;利用免疫组化法(immunohistochemical,IHC)检测临床内膜组织中PDIA3的表达水平,分析不同表达水平EC患者的临床病理参数、预后及影响其预后的危险因素;利用Transwell实验、划痕实验、CCK-8实验检测敲低PDIA3表达的Ishikawa细胞的增殖、侵袭和迁移能力。结果TCGA数据库及临床标本中EC组织PDIA3表达水平高于正常内膜组织(P<0.05),TCGA数据库中EC组织PDIA3表达水平G3级组高于G1及G2级组(P<0.05),临床标本中EC组织PDIA3表达水平国际妇产科联盟(Federation International of Gynecology and Obstetrics,FIGO)分期Ⅱ~Ⅳ期组高于Ⅰ期组、有淋巴结转移组高于无淋巴结转移组、高分化组高于低分化组(P<0.05);COX回归分析结果显示,FIGO分期、PDIA3表达水平是影响EC患者预后的独立危险因素;TCGA数据库中EC患者PDIA3高表达组生存时间短于低表达组(P<0.05),临床患者PDIA3阳性组生存率低于阴性组(P<0.05);Transwell实验、划痕实验及CCK-8实验显示PDIA3抑制组细胞的侵袭和迁移能力较正常组及阴性对照组显著降低(P<0.05)。结论PDIA3在EC组织中呈高表达,与肿瘤恶性程度和患者不良预后相关;靶向抑制PDIA3的表达可降低Ishikawa细胞的增殖、侵袭和迁移能力。展开更多
Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the ci...Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.展开更多
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
文摘目的探究蛋白质二硫键异构酶A3(protein disulfide isomerase A3,PDIA3)在子宫内膜癌(endometrial cancer,EC)组织中的表达水平、临床意义及其对Ishikawa细胞的影响。方法利用TCGA数据库分析不同内膜组织中PDIA3的表达水平差异,探究其与EC患者临床病理参数及预后间的联系;利用免疫组化法(immunohistochemical,IHC)检测临床内膜组织中PDIA3的表达水平,分析不同表达水平EC患者的临床病理参数、预后及影响其预后的危险因素;利用Transwell实验、划痕实验、CCK-8实验检测敲低PDIA3表达的Ishikawa细胞的增殖、侵袭和迁移能力。结果TCGA数据库及临床标本中EC组织PDIA3表达水平高于正常内膜组织(P<0.05),TCGA数据库中EC组织PDIA3表达水平G3级组高于G1及G2级组(P<0.05),临床标本中EC组织PDIA3表达水平国际妇产科联盟(Federation International of Gynecology and Obstetrics,FIGO)分期Ⅱ~Ⅳ期组高于Ⅰ期组、有淋巴结转移组高于无淋巴结转移组、高分化组高于低分化组(P<0.05);COX回归分析结果显示,FIGO分期、PDIA3表达水平是影响EC患者预后的独立危险因素;TCGA数据库中EC患者PDIA3高表达组生存时间短于低表达组(P<0.05),临床患者PDIA3阳性组生存率低于阴性组(P<0.05);Transwell实验、划痕实验及CCK-8实验显示PDIA3抑制组细胞的侵袭和迁移能力较正常组及阴性对照组显著降低(P<0.05)。结论PDIA3在EC组织中呈高表达,与肿瘤恶性程度和患者不良预后相关;靶向抑制PDIA3的表达可降低Ishikawa细胞的增殖、侵袭和迁移能力。
基金supported by the National Natural Science Foundation of China(Grant Nos.82073276 and 82273100)Science and Technology Project of Tianjin Binhai New Area Health Commission(Grant No.2022BWKY016)the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058).
文摘Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
