NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion(I/R)injury,and the aim of this study is to investigate the potential utilization of the Chinese medicine,Puerarin...NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion(I/R)injury,and the aim of this study is to investigate the potential utilization of the Chinese medicine,Puerarin,in treating this disease.Through conducting in vitro and in vivo experiments,the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8(DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death,resulting in the attenuation of I/R injury.Specifically,the cerebral I/R injury in rat models and hypoxia/reoxygenation(H/R)in primary hippocampus neuron(PHN)cells were inducted,which were subsequently exposed to Puerarin treatment.As expected,we validated that Puerarin suppressed cell pyroptosis and rescued cell viability in I/R rat hippocampus tissues and H/R PHN cells.Next,through bioinformatics analysis,we noticed that miR-223-3p targeted both LncRNA DUXAP8 and NLRP3 mRNA,and both LncRNA DUXAP8 ablation and miR-223-3p overexpression inactivate NLRP3-mediated cell pyroptosis to rescue cell viability in H/R PHN cells.Interestingly,we evidenced that Puerarin restrained LncRNA DUXAP8 expressions,but upregulated miR-223-3p in I/R rat tissues and H/R PHN cells,and the protective effects of Puerarin on H/R PHN cells were abrogated by overexpressing LncRNA DUXAP8 and silencing miR-223-3p.Collectively,we concluded that Puerarin regulated LncRNA DUXAP8/miR-223-3p/NLRP3 signaling cascade to attenuate I/R injury.展开更多
Background:Recent studies highlight pseudogene derived long non-coding RNAs(lncRNAs)as key regulators of cancer biology.However,few of them have been well characterized in pancreatic cancer.Here,we aimed to identify t...Background:Recent studies highlight pseudogene derived long non-coding RNAs(lncRNAs)as key regulators of cancer biology.However,few of them have been well characterized in pancreatic cancer.Here,we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells.Methods:We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by compara-tive analysis of three independent datasets from GEO.Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells.Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo.RNA immunoprecipitation,chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells.Results:Pancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues.High DUXAP8 expression was associated with a larger tumor size,advanced pathological stage and shorter overall survival of pancreatic cancer patients.Moreover,silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo.Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression.Conclusion:Our results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression.DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.展开更多
Background Lung adenocarcinoma(LUAD)is a common cancer with a poor prognosis.Platelet-activating factor acetylhydrolase,isoform Ib,gamma subunit 29 kDa(PAFAH1B3)plays an important role in the development of many types...Background Lung adenocarcinoma(LUAD)is a common cancer with a poor prognosis.Platelet-activating factor acetylhydrolase,isoform Ib,gamma subunit 29 kDa(PAFAH1B3)plays an important role in the development of many types of human malignancies.However,the precise role and mechanisms of PAFAH1B3 in LUAD are still unknown.Therefore,we will initially explore the effect of PAFAH1B3 on LUAD in this study.Methods In this study,we first performed a pan-cancer analysis of PAFAH1B3 expression and prognosis using The Cancer Genome Atlas(TCGA),genotype-tissue expression(GTEx)data,and GEPIA database.Next,the relationship between PAFAH1B3 expression and LUAD immune infiltration and pyroptosis-related genes was explored by GEPIA database and TIMER database.The effect of PAFAH1B3 on LUAD was further explored by CCK-8,wound healing,and Transwell assays.Finally,non-coding RNA(ncRNA)that may be involved in the regulation of PAFAH1B3 was explored using Starbase database analysis.Results The results found that PAFAH1B3 may be an oncogene in LUAD and has a significant adverse relationship with tumor immune cell infiltration,immune cell biomarkers and pyroptosis-related gene expression.Meanwhile,cell experiments also found that PAFAH1B3 knockout significantly reduced the proliferation,migration and invasion of A549 cells.Conclusions PAFAH1B3 high expression in LUAD patients is associated with poor prognosis,tumor immune infiltration,and cell pyroptosis gene expression.展开更多
基金supported by the Project of Scientific Research Fund of Traditional Chinese Medicine of Zhejiang Province(No.2020ZB230).
文摘NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion(I/R)injury,and the aim of this study is to investigate the potential utilization of the Chinese medicine,Puerarin,in treating this disease.Through conducting in vitro and in vivo experiments,the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8(DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death,resulting in the attenuation of I/R injury.Specifically,the cerebral I/R injury in rat models and hypoxia/reoxygenation(H/R)in primary hippocampus neuron(PHN)cells were inducted,which were subsequently exposed to Puerarin treatment.As expected,we validated that Puerarin suppressed cell pyroptosis and rescued cell viability in I/R rat hippocampus tissues and H/R PHN cells.Next,through bioinformatics analysis,we noticed that miR-223-3p targeted both LncRNA DUXAP8 and NLRP3 mRNA,and both LncRNA DUXAP8 ablation and miR-223-3p overexpression inactivate NLRP3-mediated cell pyroptosis to rescue cell viability in H/R PHN cells.Interestingly,we evidenced that Puerarin restrained LncRNA DUXAP8 expressions,but upregulated miR-223-3p in I/R rat tissues and H/R PHN cells,and the protective effects of Puerarin on H/R PHN cells were abrogated by overexpressing LncRNA DUXAP8 and silencing miR-223-3p.Collectively,we concluded that Puerarin regulated LncRNA DUXAP8/miR-223-3p/NLRP3 signaling cascade to attenuate I/R injury.
基金supported by grants from the National Natural Science Foundation of China(Nos.81602052,8160100460,and 8157040399).
文摘Background:Recent studies highlight pseudogene derived long non-coding RNAs(lncRNAs)as key regulators of cancer biology.However,few of them have been well characterized in pancreatic cancer.Here,we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells.Methods:We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by compara-tive analysis of three independent datasets from GEO.Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells.Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo.RNA immunoprecipitation,chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells.Results:Pancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues.High DUXAP8 expression was associated with a larger tumor size,advanced pathological stage and shorter overall survival of pancreatic cancer patients.Moreover,silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo.Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression.Conclusion:Our results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression.DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.
基金supported by the National Postdoctoral Innovation Talents Support Program of China,and National Natural Science Foundation of China(No.82303564).
文摘Background Lung adenocarcinoma(LUAD)is a common cancer with a poor prognosis.Platelet-activating factor acetylhydrolase,isoform Ib,gamma subunit 29 kDa(PAFAH1B3)plays an important role in the development of many types of human malignancies.However,the precise role and mechanisms of PAFAH1B3 in LUAD are still unknown.Therefore,we will initially explore the effect of PAFAH1B3 on LUAD in this study.Methods In this study,we first performed a pan-cancer analysis of PAFAH1B3 expression and prognosis using The Cancer Genome Atlas(TCGA),genotype-tissue expression(GTEx)data,and GEPIA database.Next,the relationship between PAFAH1B3 expression and LUAD immune infiltration and pyroptosis-related genes was explored by GEPIA database and TIMER database.The effect of PAFAH1B3 on LUAD was further explored by CCK-8,wound healing,and Transwell assays.Finally,non-coding RNA(ncRNA)that may be involved in the regulation of PAFAH1B3 was explored using Starbase database analysis.Results The results found that PAFAH1B3 may be an oncogene in LUAD and has a significant adverse relationship with tumor immune cell infiltration,immune cell biomarkers and pyroptosis-related gene expression.Meanwhile,cell experiments also found that PAFAH1B3 knockout significantly reduced the proliferation,migration and invasion of A549 cells.Conclusions PAFAH1B3 high expression in LUAD patients is associated with poor prognosis,tumor immune infiltration,and cell pyroptosis gene expression.
