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
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.
