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
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
BACKGROUND Endometriosis (EMs) is a chronic and recurrent,but benign,disease in women of reproductive age,and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders.The etiology of E...BACKGROUND Endometriosis (EMs) is a chronic and recurrent,but benign,disease in women of reproductive age,and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders.The etiology of EMs is not clear.Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs.MicroRNAs (miRNAs) are implicated in several biological processes,such as cell proliferation,differentiation,and apoptosis.MiR-451 is interesting,as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers.AIM To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways.METHODS Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls).Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs.MiR-451 targets were predicted using miRDB and miRcode target-predicting databases.RESULTS We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues,and this difference was not related to the American Society for Reproductive Medicine stage.Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation.SiRNA-mediated miR-451 knockdown reversed these effects.Using miRDB and miRcode,we identified 12 potential miR-451 target genes.We hypothesize that the expression of YWHAZ,OSR1,TTN,and CDKN2D may be regulated by miR- 451 and be involved in disease pathogenesis.CONCLUSION Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis.Thus,miR-451 is a novel biomarker for EMs.YWHAZ,OSR1,TTN,and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.展开更多
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
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.
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BACKGROUND Endometriosis (EMs) is a chronic and recurrent,but benign,disease in women of reproductive age,and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders.The etiology of EMs is not clear.Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs.MicroRNAs (miRNAs) are implicated in several biological processes,such as cell proliferation,differentiation,and apoptosis.MiR-451 is interesting,as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers.AIM To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways.METHODS Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls).Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs.MiR-451 targets were predicted using miRDB and miRcode target-predicting databases.RESULTS We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues,and this difference was not related to the American Society for Reproductive Medicine stage.Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation.SiRNA-mediated miR-451 knockdown reversed these effects.Using miRDB and miRcode,we identified 12 potential miR-451 target genes.We hypothesize that the expression of YWHAZ,OSR1,TTN,and CDKN2D may be regulated by miR- 451 and be involved in disease pathogenesis.CONCLUSION Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis.Thus,miR-451 is a novel biomarker for EMs.YWHAZ,OSR1,TTN,and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.
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.
