AIM：To investigate the changes in the expression of micro RNA-181a（mi R-181a）and Bim in a rat model of retinal ischemia-reperfusion（RIR）,to explore their target relationship in RIR and their involvement in regula...AIM：To investigate the changes in the expression of micro RNA-181a（mi R-181a）and Bim in a rat model of retinal ischemia-reperfusion（RIR）,to explore their target relationship in RIR and their involvement in regulating apoptosis of retinal ganglion cells（RGCs）.·M ETHODS：Target gene prediction for mi R-181a was performed with the aid of bioinformatics and Bim was identified as a potential target gene of mi R-181a.A rat model of RIR was created by increasing the intraocular pressure.RGCs in the flatmounted retinas were labeled with Brn3,a marker for alive RGCs,by immunofluorescent staining.The changes in the number of RGCs after RIR were recorded.Quantitative reverse transcription-polymerase chain reaction（q RT-PCR）was used to determine the expression level of mi R-181a in the retina.Bim/Brn3 double immunofluorescence was used to detect the localization of Bim.The expression of Bim in the retina was determined with the aids of Western blot and q RT-PCR.·R ESULTS：Compared with the negative control group,the density of RGCs was significantly lower in the ischemia/reperfusion（I/R）-24h and I/R-72h groups（〈0.001）.The expression level of mi R-181a started to decrease at 0h after RIR,and further decreased at 24h and 72h compared with the negative control group（〈0.001）.Bim was significantly upregulated at 12h after RIR（〈0.05）and reached peak at 24,72h compared with the negative control group（〈0.01）.Pearson correlation analysis showed that the expression level of Bim was negatively correlated with the expression level of mi R-181a and the density of RGCs.·CONCLUSION：Bim may be a potential target gene of mi R-181a.Both mi R-181a and Bim are involved in RGCs death in RIR.RIR may promote RGCs apoptosis in the retina downregulation of mi R-181a and its inhibition on Bim expression.展开更多
Tumor progression is usually characterized by proliferation,migration,and angiogenesis,which is essential for supplying both nutrients and oxygen to the tumor cells.Therefore,targeting angiogenesis has been considered...Tumor progression is usually characterized by proliferation,migration,and angiogenesis,which is essential for supplying both nutrients and oxygen to the tumor cells.Therefore,targeting angiogenesis has been considered a promising therapeutic strategy for cancer prevention and treatment.In the present study,we demonstrated that in addition to suppressing lung cancer cell proliferation and migration in vitro,10-hydroxycamptothecin(10-HCPT)is also capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner.Mechanistically,by upregulating miR-181a,which in turn downregulating FOXP1,10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis.Furthermore,reduced levels of miR-181a have been found in both lung cancer cell lines and xenograft with concurrently elevated levels of FOXP1,VEGF,bFGF,and HDGF.Consistent with the findings from the in vitro experiments,miR-181a impairs neovascularization in our xenograft model.In summary,our findings have not only established the anti-oncogenic role of miR-181a in lung cancer angiogenesis but also suggest that 10-HCPT could be a potential therapeutic reagent for lung cancer treatment.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Supported by the National Natural Science Foundation of China(No.81070742/H1205)the International Collaboration Foundation from the Department of Science and Technology of Sichuan Province,China(No.2010HH0030)
文摘AIM：To investigate the changes in the expression of micro RNA-181a（mi R-181a）and Bim in a rat model of retinal ischemia-reperfusion（RIR）,to explore their target relationship in RIR and their involvement in regulating apoptosis of retinal ganglion cells（RGCs）.·M ETHODS：Target gene prediction for mi R-181a was performed with the aid of bioinformatics and Bim was identified as a potential target gene of mi R-181a.A rat model of RIR was created by increasing the intraocular pressure.RGCs in the flatmounted retinas were labeled with Brn3,a marker for alive RGCs,by immunofluorescent staining.The changes in the number of RGCs after RIR were recorded.Quantitative reverse transcription-polymerase chain reaction（q RT-PCR）was used to determine the expression level of mi R-181a in the retina.Bim/Brn3 double immunofluorescence was used to detect the localization of Bim.The expression of Bim in the retina was determined with the aids of Western blot and q RT-PCR.·R ESULTS：Compared with the negative control group,the density of RGCs was significantly lower in the ischemia/reperfusion（I/R）-24h and I/R-72h groups（〈0.001）.The expression level of mi R-181a started to decrease at 0h after RIR,and further decreased at 24h and 72h compared with the negative control group（〈0.001）.Bim was significantly upregulated at 12h after RIR（〈0.05）and reached peak at 24,72h compared with the negative control group（〈0.01）.Pearson correlation analysis showed that the expression level of Bim was negatively correlated with the expression level of mi R-181a and the density of RGCs.·CONCLUSION：Bim may be a potential target gene of mi R-181a.Both mi R-181a and Bim are involved in RGCs death in RIR.RIR may promote RGCs apoptosis in the retina downregulation of mi R-181a and its inhibition on Bim expression.
基金supported by the National Natural Science Foundation of China(Nos.81702296,81772281)the Shandong Science and Technology Committee(Nos.2017GSF18124,ZR2019PC019,ZR2019MH022)+1 种基金the Health Commission of Shandong Province(Nos.2017WS737,2019KJK014)the Shandong Province Taishan Scholar Project(No.ts201712067).
文摘Tumor progression is usually characterized by proliferation,migration,and angiogenesis,which is essential for supplying both nutrients and oxygen to the tumor cells.Therefore,targeting angiogenesis has been considered a promising therapeutic strategy for cancer prevention and treatment.In the present study,we demonstrated that in addition to suppressing lung cancer cell proliferation and migration in vitro,10-hydroxycamptothecin(10-HCPT)is also capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner.Mechanistically,by upregulating miR-181a,which in turn downregulating FOXP1,10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis.Furthermore,reduced levels of miR-181a have been found in both lung cancer cell lines and xenograft with concurrently elevated levels of FOXP1,VEGF,bFGF,and HDGF.Consistent with the findings from the in vitro experiments,miR-181a impairs neovascularization in our xenograft model.In summary,our findings have not only established the anti-oncogenic role of miR-181a in lung cancer angiogenesis but also suggest that 10-HCPT could be a potential therapeutic reagent for lung cancer treatment.
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。
