[目的]探讨尿液微小RNA(miR)-30a-5p表达与肌层浸润性膀胱癌(muscule-invasive bladder cancer,MIBC)患者新辅助化疗(neoadjuvant chemotherapy,NAC)反应和预后的相关性。[方法]回顾性分析2017年11月至2020年11月咸阳市第一人民医院收治...[目的]探讨尿液微小RNA(miR)-30a-5p表达与肌层浸润性膀胱癌(muscule-invasive bladder cancer,MIBC)患者新辅助化疗(neoadjuvant chemotherapy,NAC)反应和预后的相关性。[方法]回顾性分析2017年11月至2020年11月咸阳市第一人民医院收治的91例MIBC患者的临床资料,患者均接受了基于顺铂和吉西他滨的NAC方案,然后行膀胱手术。NAC治疗2个周期后评估肿瘤反应,将患者分为化疗敏感组和化疗抵抗组。采用实时荧光定量PCR检测尿液miR-30a-5p表达水平,定量甲基化特异性聚合酶链反应评估miR-30a-5p启动子区甲基化状态。分析尿液miR-30a-5p表达水平与患者总生存期(overall survival,OS)和疾病特异性生存期(disease specific survival,DSS)的关系。[结果 ]根据尿液miR-30a-5p表达中位值(0.72)将MIBC患者分为高表达(>0.72)组和低表达(≤0.72)组,miR-30a-5p低表达组患者淋巴结转移率(P=0.039)及Ki-67指数(P<0.001)较miR-30a-5p高表达组更高,且NAC化疗抵抗率更高(P=0.027)。化疗抵抗患者尿液miR-30a-5p表达水平明显低于化疗敏感组[0.53(0.26,0.94) vs 1.93(0.71,6.32),P=0.014]。尿液miR-30a-5p表达水平(≤0.66)预测NAC化疗敏感性的受试者工作特征曲线下面积(0.792)和灵敏度(92.60%)均较高。多因素分析显示,尿液miR-30a-5p是NAC敏感的独立预测因素(OR=0.323,95%CI:0.132~0.792,P=0.013)。miR-30a-5p低表达组患者中位DSS时间(328.0 d vs 614.5 d,P=0.002)和中位OS时间(495.5 d vs 1 026.0 d,P<0.001)均短于高表达组。尿液miR-30a-5p表达水平和MIBC组织样本中miR-30a-5p启动子CpG岛的甲基化率呈负相关(r=-0.759,P<0.001)。[结论]尿液miR-30a-5p低表达与MIBC患者NAC治疗反应和不良预后有关,可作为MIBC预后和NAC反应预测的生物标志物。展开更多
BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this ...BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this disease.AIM To explore the mechanism of miR-125a-5p in the pathogenesis of GC.METHODS The expression levels of miR-125a-5p,SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction(PCR)and Western blotting.Methylation-specific PCR was used to detect the level of miR-125a-5p methylation.A cell counting kit 8 assay,scratch test,and a Transwell assay were performed to detect the proliferation,migration,and invasiveness of HGC27 cells,respectively.The expression of the epithelial mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin and vimentin in HGC27 cells was detected by Western blotting,while the expression of vimentin was detected by immunofluorescence.RESULTS This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation,migration,invasiveness and EMT of GC cells.Mechanistically,miR-125a-5p can reduce GC cell proliferation,promote E-cadherin expression,inhibit N-cadherin and vimentin expression,and reduce the EMT of GC cells,thus constraining GC cells to a certain extent.Moreover,DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter,thereby promoting the expression of SERPINE1,which acts together with miR-125a-5p to exert antagonistic effects on GC.CONCLUSION Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation,which led to the proliferation,migration and occurrence of EMT in GC cells.展开更多
文摘[目的]探讨尿液微小RNA(miR)-30a-5p表达与肌层浸润性膀胱癌(muscule-invasive bladder cancer,MIBC)患者新辅助化疗(neoadjuvant chemotherapy,NAC)反应和预后的相关性。[方法]回顾性分析2017年11月至2020年11月咸阳市第一人民医院收治的91例MIBC患者的临床资料,患者均接受了基于顺铂和吉西他滨的NAC方案,然后行膀胱手术。NAC治疗2个周期后评估肿瘤反应,将患者分为化疗敏感组和化疗抵抗组。采用实时荧光定量PCR检测尿液miR-30a-5p表达水平,定量甲基化特异性聚合酶链反应评估miR-30a-5p启动子区甲基化状态。分析尿液miR-30a-5p表达水平与患者总生存期(overall survival,OS)和疾病特异性生存期(disease specific survival,DSS)的关系。[结果 ]根据尿液miR-30a-5p表达中位值(0.72)将MIBC患者分为高表达(>0.72)组和低表达(≤0.72)组,miR-30a-5p低表达组患者淋巴结转移率(P=0.039)及Ki-67指数(P<0.001)较miR-30a-5p高表达组更高,且NAC化疗抵抗率更高(P=0.027)。化疗抵抗患者尿液miR-30a-5p表达水平明显低于化疗敏感组[0.53(0.26,0.94) vs 1.93(0.71,6.32),P=0.014]。尿液miR-30a-5p表达水平(≤0.66)预测NAC化疗敏感性的受试者工作特征曲线下面积(0.792)和灵敏度(92.60%)均较高。多因素分析显示,尿液miR-30a-5p是NAC敏感的独立预测因素(OR=0.323,95%CI:0.132~0.792,P=0.013)。miR-30a-5p低表达组患者中位DSS时间(328.0 d vs 614.5 d,P=0.002)和中位OS时间(495.5 d vs 1 026.0 d,P<0.001)均短于高表达组。尿液miR-30a-5p表达水平和MIBC组织样本中miR-30a-5p启动子CpG岛的甲基化率呈负相关(r=-0.759,P<0.001)。[结论]尿液miR-30a-5p低表达与MIBC患者NAC治疗反应和不良预后有关,可作为MIBC预后和NAC反应预测的生物标志物。
基金the Research Program of the Science and Technology Department of Yunnan Province,No.202101AY070001-204.
文摘BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this disease.AIM To explore the mechanism of miR-125a-5p in the pathogenesis of GC.METHODS The expression levels of miR-125a-5p,SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction(PCR)and Western blotting.Methylation-specific PCR was used to detect the level of miR-125a-5p methylation.A cell counting kit 8 assay,scratch test,and a Transwell assay were performed to detect the proliferation,migration,and invasiveness of HGC27 cells,respectively.The expression of the epithelial mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin and vimentin in HGC27 cells was detected by Western blotting,while the expression of vimentin was detected by immunofluorescence.RESULTS This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation,migration,invasiveness and EMT of GC cells.Mechanistically,miR-125a-5p can reduce GC cell proliferation,promote E-cadherin expression,inhibit N-cadherin and vimentin expression,and reduce the EMT of GC cells,thus constraining GC cells to a certain extent.Moreover,DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter,thereby promoting the expression of SERPINE1,which acts together with miR-125a-5p to exert antagonistic effects on GC.CONCLUSION Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation,which led to the proliferation,migration and occurrence of EMT in GC cells.
