目的:评估急诊冠状动脉介入治疗术(PCI)后循环microRNA-26b-5p水平和血糖水平变化的趋势及相关性。方法:根据入选标准和排除标准,共入选接受急诊PCI术的急性前壁心肌梗死患者38例。详细记录临床相关资料,分别于术前、术后24h、术后72h...目的:评估急诊冠状动脉介入治疗术(PCI)后循环microRNA-26b-5p水平和血糖水平变化的趋势及相关性。方法:根据入选标准和排除标准,共入选接受急诊PCI术的急性前壁心肌梗死患者38例。详细记录临床相关资料,分别于术前、术后24h、术后72h行循环血microRNA-26b-5p和血糖水平检测。Real Time PCR法检测血液样本中microRNA-26b-5p表达量的变化。结果:对于成功行急诊PCI的急性心肌梗死患者,术后microRNA-26b-5p表达水平较术前明显升高(P<0.01),术后血糖水平逐渐下降(P<0.01),两者之间存在负相关(r=-0.332,P<0.01)。结论:急性心肌梗死患者往往存在应激性高血糖,microRNA-26b-5p可能参与血糖水平的相关。展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
目的:筛选胰腺癌(PC)侵袭相关微小RNA(miRNA,miR),验证其生物学功能和调控的信号通路,为胰腺癌的诊治提供新的分子标志物和靶点。方法:通过基因表达综合数据库(GEO)的miRNA表达谱数据集GSE71533和GSE85589,分析miR-26b-5p的差异表达;利...目的:筛选胰腺癌(PC)侵袭相关微小RNA(miRNA,miR),验证其生物学功能和调控的信号通路,为胰腺癌的诊治提供新的分子标志物和靶点。方法:通过基因表达综合数据库(GEO)的miRNA表达谱数据集GSE71533和GSE85589,分析miR-26b-5p的差异表达;利用癌症基因组图谱数据库(TCGA),分析miR-26b-5p对PC患者总生存率的影响。采用TargetScan数据库识别miR-26b-5p的靶基因集。通过细胞功能实验,验证miR-26b-5p对PANC-1细胞增殖、迁移和侵袭的影响。利用基因本体(GO)和KEGG通路富集分析,揭示miR-26b-5p靶基因的功能,并通过蛋白印迹(Western blotting)实验验证miR-26b-5p靶向的信号通路。结果:在GSE71533和GSE85589数据集,相对于正常组织和对照组血浆,miR-26b-5p在PC组织和PC患者血浆明显低表达(9.65±0.10 vs 10.18±0.07,P<0.001;0.67±0.18 vs 0.79±0.24,P=0.017)。TCGA-胰腺癌生存分析结果显示,miR-26b-5p高表达组的总体生存率明显优于低表达组(P=0.023)。KEGG分析显示,预测的251个miR-26b-5p的靶基因与MAPK信号通路有关。CCK-8实验、Transwell迁移、侵袭实验和划痕实验结果显示:miR-26b-5p抑制PANC-1细胞的增殖、迁移和侵袭。KEGG通路富集分析结果提示miR-26b-5p的靶基因参与丝裂原活化蛋白激酶(MAPK)信号通路。Western blotting实验证实miR-26b-5p下调MKNK2/eIF4E信号通路。结论:miR-26b-5p下调MKNK2/eIF4E信号通路,抑制PANC-1细胞增殖、侵袭,有可能作为胰腺癌诊断和治疗的新靶点。展开更多
文摘目的:评估急诊冠状动脉介入治疗术(PCI)后循环microRNA-26b-5p水平和血糖水平变化的趋势及相关性。方法:根据入选标准和排除标准,共入选接受急诊PCI术的急性前壁心肌梗死患者38例。详细记录临床相关资料,分别于术前、术后24h、术后72h行循环血microRNA-26b-5p和血糖水平检测。Real Time PCR法检测血液样本中microRNA-26b-5p表达量的变化。结果:对于成功行急诊PCI的急性心肌梗死患者,术后microRNA-26b-5p表达水平较术前明显升高(P<0.01),术后血糖水平逐渐下降(P<0.01),两者之间存在负相关(r=-0.332,P<0.01)。结论:急性心肌梗死患者往往存在应激性高血糖,microRNA-26b-5p可能参与血糖水平的相关。
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
文摘目的:筛选胰腺癌(PC)侵袭相关微小RNA(miRNA,miR),验证其生物学功能和调控的信号通路,为胰腺癌的诊治提供新的分子标志物和靶点。方法:通过基因表达综合数据库(GEO)的miRNA表达谱数据集GSE71533和GSE85589,分析miR-26b-5p的差异表达;利用癌症基因组图谱数据库(TCGA),分析miR-26b-5p对PC患者总生存率的影响。采用TargetScan数据库识别miR-26b-5p的靶基因集。通过细胞功能实验,验证miR-26b-5p对PANC-1细胞增殖、迁移和侵袭的影响。利用基因本体(GO)和KEGG通路富集分析,揭示miR-26b-5p靶基因的功能,并通过蛋白印迹(Western blotting)实验验证miR-26b-5p靶向的信号通路。结果:在GSE71533和GSE85589数据集,相对于正常组织和对照组血浆,miR-26b-5p在PC组织和PC患者血浆明显低表达(9.65±0.10 vs 10.18±0.07,P<0.001;0.67±0.18 vs 0.79±0.24,P=0.017)。TCGA-胰腺癌生存分析结果显示,miR-26b-5p高表达组的总体生存率明显优于低表达组(P=0.023)。KEGG分析显示,预测的251个miR-26b-5p的靶基因与MAPK信号通路有关。CCK-8实验、Transwell迁移、侵袭实验和划痕实验结果显示:miR-26b-5p抑制PANC-1细胞的增殖、迁移和侵袭。KEGG通路富集分析结果提示miR-26b-5p的靶基因参与丝裂原活化蛋白激酶(MAPK)信号通路。Western blotting实验证实miR-26b-5p下调MKNK2/eIF4E信号通路。结论:miR-26b-5p下调MKNK2/eIF4E信号通路,抑制PANC-1细胞增殖、侵袭,有可能作为胰腺癌诊断和治疗的新靶点。
