目的探究糖尿病肾病(DN)患者血清miR-488,miR-654水平与疾病严重程度及预后的关系。方法选取92例2022年1月~2024年1月雅安市人民医院诊治的DN患者(DN组)以及60例健康正常人(健康组)进行miR-488,miR-654水平检测,Pearson分析血清miR-488...目的探究糖尿病肾病(DN)患者血清miR-488,miR-654水平与疾病严重程度及预后的关系。方法选取92例2022年1月~2024年1月雅安市人民医院诊治的DN患者(DN组)以及60例健康正常人(健康组)进行miR-488,miR-654水平检测,Pearson分析血清miR-488与miR-654的相关性;卡方检验分析血清miR-488,miR-654表达水平与临床病理特征和肾脏损伤程度的关系;ROC预测DN患者预后情况。结果DN患者与健康组相比,血清miR-488(1.71±0.40 vs 1.08±0.15)表达水平明显升高,miR-654(0.66±0.19 vs 0.94±0.22)表达水平明显降低,差异具有统计学意义(t=11.666,8.340,均P<0.05)。糖尿病年限≥10年、24h尿蛋白≥3 g/L、血肌酐≥150μmol/L、肾小球滤过率<60 ml/min/1.73m2,血尿素氮≥7.5mmol/L的DN患者血清miR-488高表达、miR-654低表达占比显著高于血清miR-488低表达、miR-654高表达患者,差异具有统计学意义(χ^(2)=5.283~25.234;4.356~8.587,均P<0.05)。Pearson分析DN组血清miR-488与miR-654呈负相关(r=-0.405,P<0.05);血清miR-488与24h尿蛋白、血肌酐、血尿素氮呈正相关(r=0.376,0.435,0.406,均P<0.05),与肾小球滤过率呈负相关(r=-0.382,P<0.05);血清miR-654与24h尿蛋白、血肌酐、血尿素氮呈负相关(r=-0.418,-0.367,-0.425,均P<0.05),与肾小球滤过率呈正相关(r=0.374,P<0.05)。肾小球分级Ⅳ级、间质炎症2分、间质纤维化和肾小管萎缩(IFTA)3分DN患者miR-488高表达、miR-654低表达占比显著高于miR-488低表达、miR-654高表达,差异具有统计学意义(χ^(2)=7.916~20.669,8.432~13.258,均P<0.05)。与预后不良组相比,预后良好组血清miR-488表达水平显著降低(1.57±0.29 vs 1.89±0.17),miR-654表达水平显著升高(0.78±0.21 vs 0.51±0.19),差异具有统计学意义(t=6.202,6.369,均P<0.05)。血清miR-488,miR-654单独及二者联合对DN患者预后的敏感度分别为87.50%,80.00%和90.00%,特异度分别为84.62%,86.54%和82.69%,AUC(95%CI)分别为0.838(0.748~0.927),0.824(0.731~0.916)和0.906(0.846~0.966),二者联合预测优于各自单独预测(Z=2.225,2.033,P=0.026,0.042)。结论DN患者肾脏损伤程度越低,血清miR-488表达水平越低,血清miR-654越高,血清miR-488,miR-654可用于对DN患者病情及预后预测,联合预测优于单独预测。展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
文摘目的探究糖尿病肾病(DN)患者血清miR-488,miR-654水平与疾病严重程度及预后的关系。方法选取92例2022年1月~2024年1月雅安市人民医院诊治的DN患者(DN组)以及60例健康正常人(健康组)进行miR-488,miR-654水平检测,Pearson分析血清miR-488与miR-654的相关性;卡方检验分析血清miR-488,miR-654表达水平与临床病理特征和肾脏损伤程度的关系;ROC预测DN患者预后情况。结果DN患者与健康组相比,血清miR-488(1.71±0.40 vs 1.08±0.15)表达水平明显升高,miR-654(0.66±0.19 vs 0.94±0.22)表达水平明显降低,差异具有统计学意义(t=11.666,8.340,均P<0.05)。糖尿病年限≥10年、24h尿蛋白≥3 g/L、血肌酐≥150μmol/L、肾小球滤过率<60 ml/min/1.73m2,血尿素氮≥7.5mmol/L的DN患者血清miR-488高表达、miR-654低表达占比显著高于血清miR-488低表达、miR-654高表达患者,差异具有统计学意义(χ^(2)=5.283~25.234;4.356~8.587,均P<0.05)。Pearson分析DN组血清miR-488与miR-654呈负相关(r=-0.405,P<0.05);血清miR-488与24h尿蛋白、血肌酐、血尿素氮呈正相关(r=0.376,0.435,0.406,均P<0.05),与肾小球滤过率呈负相关(r=-0.382,P<0.05);血清miR-654与24h尿蛋白、血肌酐、血尿素氮呈负相关(r=-0.418,-0.367,-0.425,均P<0.05),与肾小球滤过率呈正相关(r=0.374,P<0.05)。肾小球分级Ⅳ级、间质炎症2分、间质纤维化和肾小管萎缩(IFTA)3分DN患者miR-488高表达、miR-654低表达占比显著高于miR-488低表达、miR-654高表达,差异具有统计学意义(χ^(2)=7.916~20.669,8.432~13.258,均P<0.05)。与预后不良组相比,预后良好组血清miR-488表达水平显著降低(1.57±0.29 vs 1.89±0.17),miR-654表达水平显著升高(0.78±0.21 vs 0.51±0.19),差异具有统计学意义(t=6.202,6.369,均P<0.05)。血清miR-488,miR-654单独及二者联合对DN患者预后的敏感度分别为87.50%,80.00%和90.00%,特异度分别为84.62%,86.54%和82.69%,AUC(95%CI)分别为0.838(0.748~0.927),0.824(0.731~0.916)和0.906(0.846~0.966),二者联合预测优于各自单独预测(Z=2.225,2.033,P=0.026,0.042)。结论DN患者肾脏损伤程度越低,血清miR-488表达水平越低,血清miR-654越高,血清miR-488,miR-654可用于对DN患者病情及预后预测,联合预测优于单独预测。
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
