Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor developme...Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor development and progression.The present study leverages the in-silico and in-vitro techniques to investigate the significance of hsa-miR-181a-5p and the underlying hsa-miR-181a-5p-meidated signaling pathway in glioblastoma development.Methods:Bioinformatic studies were performed on GSE158284,GSE108474(REMBRANDT study),TCGA-GTEx,CCLE,GeneMANIA,Reactome,WikiPathways,KEGG,miRDB,and microT-CDS to identify the significance of hsa-miR-181a-5p and its underlying target.Afterward,the U373 cell line was selected and transfected with hsa-miR-181a-5p mimics,and the cell viability,clonogenicity,migration,mRNA expression,apoptosis,and cell cycle were studied using the MTT assay,colony formation test,migration assay,qRT-PCR,andflow cytometry respectively.Results:hsa-miR-181a-5p expression is decreased in glioblastoma samples.The in-silico results have shown that hsa-miR-181a-5p could regulate the MAPK pathway by targeting AKT3.The experimental assays have shown that hsa-miR-181a-5p decreases the migration of glioblastoma cells,arrests the cell cycle,and increases the apoptosis rate.Besides downregulating MMP9 and upregulating BAX,hsa-miR-181a-5p downregulates MET,MAP2K1,MAPK1,MAPK3,and AKT3 expression in U373 cells.The in-vitro results were consistent with in-silico results regarding the regulatory effect of hsa-miR-181a-5p on the MAPK pathway,leading to tumor suppression in glioblastoma.Conclusions:hsa-miR-181a-5p inhibits glioblastoma development partially by regulating the signaling factors of the MAPK pathway.展开更多
目的探讨血清微小核糖核酸-503(miR-503)和微小核糖核酸-520h(miR-520h)对妊娠期糖尿病(GDM)患者并发子痫前期(PE)的诊断价值。方法选取2019年12月至2021年12月于唐山中心医院产科定期产检并建档的GDM患者102例作为研究对象,根据疾病类...目的探讨血清微小核糖核酸-503(miR-503)和微小核糖核酸-520h(miR-520h)对妊娠期糖尿病(GDM)患者并发子痫前期(PE)的诊断价值。方法选取2019年12月至2021年12月于唐山中心医院产科定期产检并建档的GDM患者102例作为研究对象,根据疾病类型分为GDM+PE组(53例)、GDM组(49例)。另选取同期于唐山中心医院进行定期产检并分娩的57例健康孕妇作为正常妊娠组。比较3组糖脂代谢相关指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、空腹胰岛素(FINS)、空腹血糖(FBG)、餐后2 h血糖(2 h PG)]水平及血清miR-503、miR-520h表达水平、血清胱抑素C(CysC)、同型半胱氨酸(Hcy)水平;比较3组不良妊娠结局。采用多因素Logistic回归分析GDM患者并发PE的危险因素;绘制受试者工作特征(ROC)曲线分析miR-503、miR-520h单独及2项指标联合检测对GDM并发PE的诊断价值。结果3组孕周、年龄、孕前体质量指数、LDL-C水平比较,差异均无统计学意义(P>0.05)。GDM+PE组TC、TG、FFA水平均明显高于GDM组和正常妊娠组,HDL-C水平明显低于GDM组和正常妊娠组,差异均有统计学意义(P<0.05)。GDM组TC、FFA水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组和GDM组FINS、FBG、2 h PG、HbA1c水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组血清miR-503、miR-520h表达水平、CysC和Hcy水平均明显高于GDM组和正常妊娠组,差异均有统计学意义(P<0.05),GDM组血清miR-503、miR-520h表达水平及CysC和Hcy水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组不良妊娠结局总发生率为62.26%(33/53),GDM组为40.82%(20/49),正常妊娠组为10.53%(6/57),GDM+PE组不良妊娠结局总发生率明显高于GDM组和正常妊娠组,差异均有统计学意义(χ^(2)=4.692、32.125,P<0.05),GDM组不良妊娠结局总发生率明显高于正常妊娠组,差异有统计学意义(χ^(2)=13.059,P<0.05)。3组孕妇不良妊娠结局中产后出血、早产或过期产、胎盘早剥、新生儿窒息、宫内生长受限的发生率比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,CysC水平升高、Hcy水平升高、miR-503表达水平升高和miR-520h表达水平升高均为GDM并发PE的危险因素(P<0.05)。ROC曲线分析结果显示,血清miR-503、miR-520h单独及2项指标联合检测诊断GDM并发PE的曲线下面积(AUC)分别为0.755、0.847、0.935,2项指标联合检测的AUC大于miR-503、miR-520h单独检测(Z_(2项联合-miR-503)=4.210、Z_(2项联合-miR-520h)=2.708,P<0.001、0.007)。结论GDM并发PE患者血清miR-503、miR-520h表达水平升高,与妊娠不良结局呈正相关,二者联合检测对诊断GDM并发PE具有重要意义。展开更多
文摘Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor development and progression.The present study leverages the in-silico and in-vitro techniques to investigate the significance of hsa-miR-181a-5p and the underlying hsa-miR-181a-5p-meidated signaling pathway in glioblastoma development.Methods:Bioinformatic studies were performed on GSE158284,GSE108474(REMBRANDT study),TCGA-GTEx,CCLE,GeneMANIA,Reactome,WikiPathways,KEGG,miRDB,and microT-CDS to identify the significance of hsa-miR-181a-5p and its underlying target.Afterward,the U373 cell line was selected and transfected with hsa-miR-181a-5p mimics,and the cell viability,clonogenicity,migration,mRNA expression,apoptosis,and cell cycle were studied using the MTT assay,colony formation test,migration assay,qRT-PCR,andflow cytometry respectively.Results:hsa-miR-181a-5p expression is decreased in glioblastoma samples.The in-silico results have shown that hsa-miR-181a-5p could regulate the MAPK pathway by targeting AKT3.The experimental assays have shown that hsa-miR-181a-5p decreases the migration of glioblastoma cells,arrests the cell cycle,and increases the apoptosis rate.Besides downregulating MMP9 and upregulating BAX,hsa-miR-181a-5p downregulates MET,MAP2K1,MAPK1,MAPK3,and AKT3 expression in U373 cells.The in-vitro results were consistent with in-silico results regarding the regulatory effect of hsa-miR-181a-5p on the MAPK pathway,leading to tumor suppression in glioblastoma.Conclusions:hsa-miR-181a-5p inhibits glioblastoma development partially by regulating the signaling factors of the MAPK pathway.
文摘目的探讨血清微小核糖核酸-503(miR-503)和微小核糖核酸-520h(miR-520h)对妊娠期糖尿病(GDM)患者并发子痫前期(PE)的诊断价值。方法选取2019年12月至2021年12月于唐山中心医院产科定期产检并建档的GDM患者102例作为研究对象,根据疾病类型分为GDM+PE组(53例)、GDM组(49例)。另选取同期于唐山中心医院进行定期产检并分娩的57例健康孕妇作为正常妊娠组。比较3组糖脂代谢相关指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、空腹胰岛素(FINS)、空腹血糖(FBG)、餐后2 h血糖(2 h PG)]水平及血清miR-503、miR-520h表达水平、血清胱抑素C(CysC)、同型半胱氨酸(Hcy)水平;比较3组不良妊娠结局。采用多因素Logistic回归分析GDM患者并发PE的危险因素;绘制受试者工作特征(ROC)曲线分析miR-503、miR-520h单独及2项指标联合检测对GDM并发PE的诊断价值。结果3组孕周、年龄、孕前体质量指数、LDL-C水平比较,差异均无统计学意义(P>0.05)。GDM+PE组TC、TG、FFA水平均明显高于GDM组和正常妊娠组,HDL-C水平明显低于GDM组和正常妊娠组,差异均有统计学意义(P<0.05)。GDM组TC、FFA水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组和GDM组FINS、FBG、2 h PG、HbA1c水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组血清miR-503、miR-520h表达水平、CysC和Hcy水平均明显高于GDM组和正常妊娠组,差异均有统计学意义(P<0.05),GDM组血清miR-503、miR-520h表达水平及CysC和Hcy水平均明显高于正常妊娠组,差异均有统计学意义(P<0.05)。GDM+PE组不良妊娠结局总发生率为62.26%(33/53),GDM组为40.82%(20/49),正常妊娠组为10.53%(6/57),GDM+PE组不良妊娠结局总发生率明显高于GDM组和正常妊娠组,差异均有统计学意义(χ^(2)=4.692、32.125,P<0.05),GDM组不良妊娠结局总发生率明显高于正常妊娠组,差异有统计学意义(χ^(2)=13.059,P<0.05)。3组孕妇不良妊娠结局中产后出血、早产或过期产、胎盘早剥、新生儿窒息、宫内生长受限的发生率比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,CysC水平升高、Hcy水平升高、miR-503表达水平升高和miR-520h表达水平升高均为GDM并发PE的危险因素(P<0.05)。ROC曲线分析结果显示,血清miR-503、miR-520h单独及2项指标联合检测诊断GDM并发PE的曲线下面积(AUC)分别为0.755、0.847、0.935,2项指标联合检测的AUC大于miR-503、miR-520h单独检测(Z_(2项联合-miR-503)=4.210、Z_(2项联合-miR-520h)=2.708,P<0.001、0.007)。结论GDM并发PE患者血清miR-503、miR-520h表达水平升高,与妊娠不良结局呈正相关,二者联合检测对诊断GDM并发PE具有重要意义。
