This study aims to detect the expression of selected circulating microRNAs(miRNA),including miRNA-451a,miRNA-486-5p and miR-10b-5p,and their prospective roles as biomarkers in patients with atherosclerosis.For this pu...This study aims to detect the expression of selected circulating microRNAs(miRNA),including miRNA-451a,miRNA-486-5p and miR-10b-5p,and their prospective roles as biomarkers in patients with atherosclerosis.For this purpose,levels of miRNAs were detected by real-time quantitative polymerase chain reaction(RT-qPCR)in case(N=30)and healthy control(N=30)groups.Receiver operating characteristic(ROC)curve analysis was carried out to evaluate the diagnostic ability of miRNAs.The correlations of miR-451a with lipid parameters were evaluated using Pearson’s correlation coefficients.HUVEC tested by ox-LDL was used as a cellular model of atherosclerosis.Cell viability and apoptosis were detected by methyl thiazolyl tetrazolium(MTT)and flow cytometry(FC)assays.Luciferase assay was used to determine the miRNA binding site on target genes.The results showed that miRNA-451a expression level was significantly lower in patients than controls.ROC curve analysis showed that the areas under the curve(AUC)of plasma miRNA-451a was 0.90.The miRNA-451a expression level exhibited significant negative correlations with cholesterol(TC),triglyceride(TG),and low-density lipoprotein(LDL).Besides,miRNA-451a specifically binds to the 3’UTR of macrophage migration inhibitory factor(MIF)and mediated the cell proliferation and apoptosis of HUVECs exposed to ox-LDL.Furthermore,overexpression of miRNA-451a promoted the proliferation and alleviated apoptosis of HUVECs exposed to ox-LDL,while this result was attenuated by macrophage migration inhibitory factor(MIF)overexpression.Therefore,miRNA-451a could be considered as a potential biomarker for atherosclerosis and miRNA-451a might contribute to regulating atherosclerosis through targeting MIF.展开更多
Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechan...Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.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
目的探讨microRNA-451(miR-451)在食管癌患者血清中的表达水平及其对早期诊断及非手术治疗疗效的判断价值。方法采用实时荧光定量PCR方法检测50例食管癌患者放疗前、后及20例健康对照者血清中miR-451的相对表达量,分析其与临床病理参数...目的探讨microRNA-451(miR-451)在食管癌患者血清中的表达水平及其对早期诊断及非手术治疗疗效的判断价值。方法采用实时荧光定量PCR方法检测50例食管癌患者放疗前、后及20例健康对照者血清中miR-451的相对表达量,分析其与临床病理参数及近期疗效的关系。结果食管癌患者血清中miR-451的表达水平明显高于健康对照者(P<0.05),miR-451的ROC曲线下面积(area under the curve,AUC)值取0.911(95%CI=0.844~0.977)时,对食管癌诊断的灵敏度和特异度分别为88%和85%。miR-451的表达水平与食管癌患者的临床分期和淋巴结转移有关。食管癌患者放疗后miR-451表达水平下降(P<0.05),且miR-451的表达水平动态变化与食管癌治疗疗效一致,有效患者miR-451表达水平下降明显高于无效患者(P<0.05)。结论血清miR-451可能对食管癌的早期诊断及非手术治疗疗效的判断有一定的参考价值。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
目的探讨microRNA-451(miR-451)在弥漫性大B细胞淋巴瘤(diffuse large B lymphoma,DLBCL)患者血浆中的表达水平及其临床意义。方法利用逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RTPCR)方法检测27例DLBCL患...目的探讨microRNA-451(miR-451)在弥漫性大B细胞淋巴瘤(diffuse large B lymphoma,DLBCL)患者血浆中的表达水平及其临床意义。方法利用逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RTPCR)方法检测27例DLBCL患者和27例健康体检者血浆中miR-451的表达水平,并统计分析DLBCL患者血浆中miR-451表达水平与临床病理参数之间的关系。结果 miR-451在DLBCL患者血浆中表达水平明显低于正常对照组[(0.41±0.15)vs.(0.64±0.21)],二者差异具有统计学意义(P<0.01);DLBCL患者血浆中miR-451表达水平在不同性别、年龄、血清LDH水平及原发部位之间差异无统计学意义(P>0.05),而与Ann Arbor分期及IPI评分明显相关(P<0.05)。结论 DLBCL患者血浆中miR-451表达水平降低,可能参与了DLBCL的病理过程。展开更多
文摘This study aims to detect the expression of selected circulating microRNAs(miRNA),including miRNA-451a,miRNA-486-5p and miR-10b-5p,and their prospective roles as biomarkers in patients with atherosclerosis.For this purpose,levels of miRNAs were detected by real-time quantitative polymerase chain reaction(RT-qPCR)in case(N=30)and healthy control(N=30)groups.Receiver operating characteristic(ROC)curve analysis was carried out to evaluate the diagnostic ability of miRNAs.The correlations of miR-451a with lipid parameters were evaluated using Pearson’s correlation coefficients.HUVEC tested by ox-LDL was used as a cellular model of atherosclerosis.Cell viability and apoptosis were detected by methyl thiazolyl tetrazolium(MTT)and flow cytometry(FC)assays.Luciferase assay was used to determine the miRNA binding site on target genes.The results showed that miRNA-451a expression level was significantly lower in patients than controls.ROC curve analysis showed that the areas under the curve(AUC)of plasma miRNA-451a was 0.90.The miRNA-451a expression level exhibited significant negative correlations with cholesterol(TC),triglyceride(TG),and low-density lipoprotein(LDL).Besides,miRNA-451a specifically binds to the 3’UTR of macrophage migration inhibitory factor(MIF)and mediated the cell proliferation and apoptosis of HUVECs exposed to ox-LDL.Furthermore,overexpression of miRNA-451a promoted the proliferation and alleviated apoptosis of HUVECs exposed to ox-LDL,while this result was attenuated by macrophage migration inhibitory factor(MIF)overexpression.Therefore,miRNA-451a could be considered as a potential biomarker for atherosclerosis and miRNA-451a might contribute to regulating atherosclerosis through targeting MIF.
基金supported by the tenth batch of"3221"industrial innovation and scientific research projects in Bengbu City(beng talent[2020]No.8)the 2021 Bengbu Medical College Science and Technology Project[Natural Science,Project Number:2021byzd217].
文摘Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.
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.
文摘目的探讨microRNA-451(miR-451)在食管癌患者血清中的表达水平及其对早期诊断及非手术治疗疗效的判断价值。方法采用实时荧光定量PCR方法检测50例食管癌患者放疗前、后及20例健康对照者血清中miR-451的相对表达量,分析其与临床病理参数及近期疗效的关系。结果食管癌患者血清中miR-451的表达水平明显高于健康对照者(P<0.05),miR-451的ROC曲线下面积(area under the curve,AUC)值取0.911(95%CI=0.844~0.977)时,对食管癌诊断的灵敏度和特异度分别为88%和85%。miR-451的表达水平与食管癌患者的临床分期和淋巴结转移有关。食管癌患者放疗后miR-451表达水平下降(P<0.05),且miR-451的表达水平动态变化与食管癌治疗疗效一致,有效患者miR-451表达水平下降明显高于无效患者(P<0.05)。结论血清miR-451可能对食管癌的早期诊断及非手术治疗疗效的判断有一定的参考价值。
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。
