目的:探讨miR-2355-3p、miR-337-3p和miR-99a-5p在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)早期筛查中的价值。方法:收集2023年7月至2024年7月在上海交通大学医学院附属第九人民医院首次就诊的60例HNSCC患者(HN...目的:探讨miR-2355-3p、miR-337-3p和miR-99a-5p在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)早期筛查中的价值。方法:收集2023年7月至2024年7月在上海交通大学医学院附属第九人民医院首次就诊的60例HNSCC患者(HNSCC组)及60例健康体检人群(正常对照组)的血清样本及临床病理资料,以平行检测方式检测miR-2355-3p、miR-337-3p和miR-99a-5p的相对表达量。采用受试者操作特征(receiver operating characteristic,ROC)曲线评估3种miRNA对HNSCC的筛查、诊断效能。结果:相较于正常对照组,HNSCC组患者血清中miR-2355-3p和miR-337-3p的表达显著上调(P<0.001),而miR-99a-5p的表达显著下调(P=0.002)。肿瘤>2 cm与≤2 cm、肿瘤分期Ⅰ-Ⅱ期与Ⅲ-Ⅳ期、有及无颈部淋巴结转移的HNSCC患者间,血清中miR-2355-3p及miR-337-3p的表达量差异有统计学意义(P<0.05),不同年龄和性别的HNSCC患者血清中3种miRNA的表达量差异均无统计学意义(P>0.05)。miR-2355-3p、miR-337-3p及miR-99a-5p单项检测诊断HNSCC的最佳截断值分别为0.0867、0.1031和0.1251,曲线下面积(area under the curve,AUC)分别为0.892、0.877和0.686。3项miRNA联合检测的AUC(0.954)在高于各单项检测的AUC(P<0.05)的同时,还高于miR-2355-3p、miR-337-3p 2项联合检测的AUC(0.898)(P<0.05)。3项miRNA联合检测早期筛查Ⅰ-Ⅱ期HNSCC的AUC为0.923。结论:miR-2355-3p和miR-337-3p与HNSCC肿瘤的分期、大小及淋巴结转移相关,miR-2355-3p、miR-337-3p及miR-99a-5p联合检测可能用于HNSCC早期筛查。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miR-2355-3p、miR-337-3p和miR-99a-5p在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)早期筛查中的价值。方法:收集2023年7月至2024年7月在上海交通大学医学院附属第九人民医院首次就诊的60例HNSCC患者(HNSCC组)及60例健康体检人群(正常对照组)的血清样本及临床病理资料,以平行检测方式检测miR-2355-3p、miR-337-3p和miR-99a-5p的相对表达量。采用受试者操作特征(receiver operating characteristic,ROC)曲线评估3种miRNA对HNSCC的筛查、诊断效能。结果:相较于正常对照组,HNSCC组患者血清中miR-2355-3p和miR-337-3p的表达显著上调(P<0.001),而miR-99a-5p的表达显著下调(P=0.002)。肿瘤>2 cm与≤2 cm、肿瘤分期Ⅰ-Ⅱ期与Ⅲ-Ⅳ期、有及无颈部淋巴结转移的HNSCC患者间,血清中miR-2355-3p及miR-337-3p的表达量差异有统计学意义(P<0.05),不同年龄和性别的HNSCC患者血清中3种miRNA的表达量差异均无统计学意义(P>0.05)。miR-2355-3p、miR-337-3p及miR-99a-5p单项检测诊断HNSCC的最佳截断值分别为0.0867、0.1031和0.1251,曲线下面积(area under the curve,AUC)分别为0.892、0.877和0.686。3项miRNA联合检测的AUC(0.954)在高于各单项检测的AUC(P<0.05)的同时,还高于miR-2355-3p、miR-337-3p 2项联合检测的AUC(0.898)(P<0.05)。3项miRNA联合检测早期筛查Ⅰ-Ⅱ期HNSCC的AUC为0.923。结论:miR-2355-3p和miR-337-3p与HNSCC肿瘤的分期、大小及淋巴结转移相关,miR-2355-3p、miR-337-3p及miR-99a-5p联合检测可能用于HNSCC早期筛查。
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.