BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediat...BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediated apoptosis in high glucose(HG)-induced primary rat kidney cells(PRKs),with emphasis on the role of miR-503 and sirtuin 4(SIRT4)in this process.METHODS Single intraperitoneal injection of streptozotocin(65 mg/kg)in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model.Glucose-treated PRKs were used as an in vitro HG model.An immunofluorescence assay identified isolated PRKs.Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis,respectively.Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stressrelated proteins.Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.RESULTS ICA treatment alleviated the upregulated miR-503 expression in vivo(DN)and in vitro(HG).Mechanistically,ICA reduced HG-induced miR-503 overexpression,thereby counteracting its function in downregulating SIRT4 levels.ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.CONCLUSION ICA reduced HG-mediated inhibition of cell viability,promotion of apoptosis,and ER stress in PRKs.These effects involved regulation of the miR-503/SIRT4 axis.These findings indicate the potential of ICA to treat DN,and implicate miR-503 as a viable target for therapeutic interventions in DN.展开更多
目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访1...目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访16个月,记录患者的预后生存结局,多因素逐步Logistic回归分析结直肠癌患者手术预后的影响因素,评估血清miR-21、miR-193a-3p对结直肠癌患者预后的预测效能。结果112例结直肠癌患者死亡22例,病死率为19.64%;生存90例,生存率为80.36%。死亡组术前血清miR-21 mRNA相对表达量、临床分期Ⅲ期占比、淋巴结转移率均高于生存组(P<0.05),血清miR-193a-3p m RNA相对表达量低于生存组(P<0.05)。多因素逐步Logistic回归分析结果显示,临床分期Ⅲ期[OR=3.777(95%CI:1.399,10.194)]、淋巴结转移[OR=5.099(95%CI:1.715,15.156)]、miR-21表达升高[OR=4.889(95%CI:1.645,14.533)]、miR-193a-3p表达降低[OR=4.402(95%CI:1.481,13.084)]均是直肠癌患者预后的影响因素(P<0.05)。受试者工作特性曲线分析结果显示,血清miR-21、miR-193a-3p单一及联合预测结直肠癌预后的敏感性分别为69.04%(95%CI:0.487,0.813)、72.73%(95%CI:0.495,0.884)、86.36%(95%CI:0.640,0.964),特异性分别为62.22%(95%CI:0.513,0.720)、68.89%(95%CI:0.581,0.780)、90.00%(95%CI:0.814,0.950),曲线下面积分别为0.782、0.731和0.901。结论结直肠癌患者术前miR-21、miR-193a-3p表达与术后预后密切相关,且在结直肠癌患者的预后结局中表现出良好的预测效能。展开更多
基金The First Affiliated Hospital of Guangzhou University of Chinese Medicine Innovation and Strengthening Fund,No.2019QN14.
文摘BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediated apoptosis in high glucose(HG)-induced primary rat kidney cells(PRKs),with emphasis on the role of miR-503 and sirtuin 4(SIRT4)in this process.METHODS Single intraperitoneal injection of streptozotocin(65 mg/kg)in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model.Glucose-treated PRKs were used as an in vitro HG model.An immunofluorescence assay identified isolated PRKs.Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis,respectively.Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stressrelated proteins.Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.RESULTS ICA treatment alleviated the upregulated miR-503 expression in vivo(DN)and in vitro(HG).Mechanistically,ICA reduced HG-induced miR-503 overexpression,thereby counteracting its function in downregulating SIRT4 levels.ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.CONCLUSION ICA reduced HG-mediated inhibition of cell viability,promotion of apoptosis,and ER stress in PRKs.These effects involved regulation of the miR-503/SIRT4 axis.These findings indicate the potential of ICA to treat DN,and implicate miR-503 as a viable target for therapeutic interventions in DN.
文摘目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访16个月,记录患者的预后生存结局,多因素逐步Logistic回归分析结直肠癌患者手术预后的影响因素,评估血清miR-21、miR-193a-3p对结直肠癌患者预后的预测效能。结果112例结直肠癌患者死亡22例,病死率为19.64%;生存90例,生存率为80.36%。死亡组术前血清miR-21 mRNA相对表达量、临床分期Ⅲ期占比、淋巴结转移率均高于生存组(P<0.05),血清miR-193a-3p m RNA相对表达量低于生存组(P<0.05)。多因素逐步Logistic回归分析结果显示,临床分期Ⅲ期[OR=3.777(95%CI:1.399,10.194)]、淋巴结转移[OR=5.099(95%CI:1.715,15.156)]、miR-21表达升高[OR=4.889(95%CI:1.645,14.533)]、miR-193a-3p表达降低[OR=4.402(95%CI:1.481,13.084)]均是直肠癌患者预后的影响因素(P<0.05)。受试者工作特性曲线分析结果显示,血清miR-21、miR-193a-3p单一及联合预测结直肠癌预后的敏感性分别为69.04%(95%CI:0.487,0.813)、72.73%(95%CI:0.495,0.884)、86.36%(95%CI:0.640,0.964),特异性分别为62.22%(95%CI:0.513,0.720)、68.89%(95%CI:0.581,0.780)、90.00%(95%CI:0.814,0.950),曲线下面积分别为0.782、0.731和0.901。结论结直肠癌患者术前miR-21、miR-193a-3p表达与术后预后密切相关,且在结直肠癌患者的预后结局中表现出良好的预测效能。
