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
目的研究脑小血管病(Cerebral small vessel disease,CSVD)患者中miR-106b-5p和高迁移率族蛋白B1(High mobility group B1,HMGB1)的表达特点,及其与血脑屏障(Blood-brain barrier,BBB)损伤的关系。方法选取2023年10月—2024年10月来中...目的研究脑小血管病(Cerebral small vessel disease,CSVD)患者中miR-106b-5p和高迁移率族蛋白B1(High mobility group B1,HMGB1)的表达特点,及其与血脑屏障(Blood-brain barrier,BBB)损伤的关系。方法选取2023年10月—2024年10月来中国人民解放军海军青岛特勤疗养中心就诊的95例CSVD患者为病例组,剔除5例临床资料不全,最终纳入90例CSVD患者。同时选取同期年龄、性别匹配的90例健康体检人群为健康组。分析2组miR-106b-5p和HMGB1的表达特点。根据病例组是否发生BBB损伤,分为有损伤患者(26例)、无损伤患者(64例)。多元Logistic分析CSVD患者发生BBB损伤的影响因素;ROC分析影响因素的预测效能;利用Pearson分析影响因素与BBB损伤的相关性;生物信息学分析miR-106b-5p、HMGB1的靶向关系。结果健康组miR-106b-5p、HMGB1显著低于病例组(P<0.05);BBB有损伤患者的miR-106b-5p、HMGB1水平显著高于无损伤患者(P<0.05);有损伤患者具有年龄、患高脂血症、脑微出血和脑白质疏松占比、基线NIHSS、深部白质Fazelus评分以及胆固醇、低密度脂蛋白、同型半胱氨酸、miR-106b-5p、HMGB1水平高的特点(P<0.05)。多元Logistic分析显示,年龄、高脂血症、基线NIHSS评分、CSVD脑白质疏松表型、深部白质Fazelus评分、miR-106b-5p、HMGB1是CSVD患者发生BBB损伤的危险因素;构建综合预测模型,ROC分析显示其具有较高的预测价值。Pearson相关性分析显示,基线NIHSS评分、CSVD脑白质疏松表型、深部白质Fazelus评分、miR-106b-5p、HMGB1均与BBB损伤呈正相关(P<0.05)。生物信息学分析表明,miR-106b-5p、HMGB1之间存在靶向关系。结论miR-106b-5p、HMGB1在CSVD患者中表达上调,并与BBB损伤呈正相关,且miR-106b-5p与HMGB1之间存在靶向关系,可作为潜在的早期诊断标志物用于临床防控和检测。展开更多
[目的]探讨miR-106b-5p的3'-末端2'-O-甲基化修饰在乳腺癌细胞中的影响。[方法]纳入2019年9月-2021年9月收治的乳腺癌患者,收集其乳腺癌组织和癌旁组织。敲低或过表达miR-106b-5p后,检测乳腺癌细胞的增值水平。乳腺癌和癌旁组...[目的]探讨miR-106b-5p的3'-末端2'-O-甲基化修饰在乳腺癌细胞中的影响。[方法]纳入2019年9月-2021年9月收治的乳腺癌患者,收集其乳腺癌组织和癌旁组织。敲低或过表达miR-106b-5p后,检测乳腺癌细胞的增值水平。乳腺癌和癌旁组织中纯化的miR-106b-5p进行质谱分析以确定分子质量和LC-MS/MS确定核苷修饰。分析甲基转移酶HENMT1对miR-106b-5p的3'-末端2'-O-甲基化作用。[结果]敲低miR-106b-5p后,乳腺癌细胞的增值水平下降(P<0.05)。乳腺组织中miR-106b-5p的3'-末端2'-O-甲基化显著高于癌旁中的水平(P<0.05)。敲低HENMT1后,乳腺癌细胞MCF7中miR-106b-5p的3'-末端2'-O-甲基化水平下降(P<0.05)。敲低HENMT1后,miR-106b-5p的半衰期下降(P<0.05)。[结论]HENMT1能对miR-106b-5p进行3'-末端2'-O-甲基化修饰(65.32±16.40 vs 11.49±3.20)。3'-末端2'-O-甲基化能提升miR-106b-5p的半衰期(0.79±0.05 vs 0.98±0.07)并促进miR-106b-5p的促乳腺癌细胞增殖(1.70±0.08 vs 1.04±0.06)。展开更多
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
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.
文摘目的研究脑小血管病(Cerebral small vessel disease,CSVD)患者中miR-106b-5p和高迁移率族蛋白B1(High mobility group B1,HMGB1)的表达特点,及其与血脑屏障(Blood-brain barrier,BBB)损伤的关系。方法选取2023年10月—2024年10月来中国人民解放军海军青岛特勤疗养中心就诊的95例CSVD患者为病例组,剔除5例临床资料不全,最终纳入90例CSVD患者。同时选取同期年龄、性别匹配的90例健康体检人群为健康组。分析2组miR-106b-5p和HMGB1的表达特点。根据病例组是否发生BBB损伤,分为有损伤患者(26例)、无损伤患者(64例)。多元Logistic分析CSVD患者发生BBB损伤的影响因素;ROC分析影响因素的预测效能;利用Pearson分析影响因素与BBB损伤的相关性;生物信息学分析miR-106b-5p、HMGB1的靶向关系。结果健康组miR-106b-5p、HMGB1显著低于病例组(P<0.05);BBB有损伤患者的miR-106b-5p、HMGB1水平显著高于无损伤患者(P<0.05);有损伤患者具有年龄、患高脂血症、脑微出血和脑白质疏松占比、基线NIHSS、深部白质Fazelus评分以及胆固醇、低密度脂蛋白、同型半胱氨酸、miR-106b-5p、HMGB1水平高的特点(P<0.05)。多元Logistic分析显示,年龄、高脂血症、基线NIHSS评分、CSVD脑白质疏松表型、深部白质Fazelus评分、miR-106b-5p、HMGB1是CSVD患者发生BBB损伤的危险因素;构建综合预测模型,ROC分析显示其具有较高的预测价值。Pearson相关性分析显示,基线NIHSS评分、CSVD脑白质疏松表型、深部白质Fazelus评分、miR-106b-5p、HMGB1均与BBB损伤呈正相关(P<0.05)。生物信息学分析表明,miR-106b-5p、HMGB1之间存在靶向关系。结论miR-106b-5p、HMGB1在CSVD患者中表达上调,并与BBB损伤呈正相关,且miR-106b-5p与HMGB1之间存在靶向关系,可作为潜在的早期诊断标志物用于临床防控和检测。
文摘[目的]探讨miR-106b-5p的3'-末端2'-O-甲基化修饰在乳腺癌细胞中的影响。[方法]纳入2019年9月-2021年9月收治的乳腺癌患者,收集其乳腺癌组织和癌旁组织。敲低或过表达miR-106b-5p后,检测乳腺癌细胞的增值水平。乳腺癌和癌旁组织中纯化的miR-106b-5p进行质谱分析以确定分子质量和LC-MS/MS确定核苷修饰。分析甲基转移酶HENMT1对miR-106b-5p的3'-末端2'-O-甲基化作用。[结果]敲低miR-106b-5p后,乳腺癌细胞的增值水平下降(P<0.05)。乳腺组织中miR-106b-5p的3'-末端2'-O-甲基化显著高于癌旁中的水平(P<0.05)。敲低HENMT1后,乳腺癌细胞MCF7中miR-106b-5p的3'-末端2'-O-甲基化水平下降(P<0.05)。敲低HENMT1后,miR-106b-5p的半衰期下降(P<0.05)。[结论]HENMT1能对miR-106b-5p进行3'-末端2'-O-甲基化修饰(65.32±16.40 vs 11.49±3.20)。3'-末端2'-O-甲基化能提升miR-106b-5p的半衰期(0.79±0.05 vs 0.98±0.07)并促进miR-106b-5p的促乳腺癌细胞增殖(1.70±0.08 vs 1.04±0.06)。
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。
