目的探讨微小RNA-214-5p(miR-214-5p)对神经母细胞瘤(NB)DNA损伤和化疗敏感性的调控作用及机制。方法通过TARGET数据库分析范可尼贫血互补组A型(fanconi anemia complementary group A protein,FACNA)蛋白与NB临床病理特征的关系。构建m...目的探讨微小RNA-214-5p(miR-214-5p)对神经母细胞瘤(NB)DNA损伤和化疗敏感性的调控作用及机制。方法通过TARGET数据库分析范可尼贫血互补组A型(fanconi anemia complementary group A protein,FACNA)蛋白与NB临床病理特征的关系。构建miR-214-5p低表达、FANCA过/低表达NB细胞系,采用细胞计数试剂盒-8(CCK-8)、移植瘤模型检测其表达对NB体内外增殖的影响,并验证miR-214-5p与FANCA靶向关系。结果GEO数据库和TARGET数据库中筛查出与NB相关的交集基因为FANCA,其表达与调节细胞增殖基因、预后及临床病理特征密切相关(P<0.05)。与空载体(Vector)组比较,FANCA组细胞活力、移植瘤体积和重量升高(P<0.05);与shNC组比较,shFANCA1组、shFANCA2组细胞活力降低(P<0.05);与对照组比较,1 mmol/L过氧化氢(H_(2)O_(2))处理后磷酸化组蛋白γ-H2AX升高(P<0.05),但FANCA过表达后γ-H2AX降低(P<0.05)。随着多柔比星浓度增加,细胞活力降低,但FANCA组细胞活力高于Vector组(P<0.05)。miR-214-5p与FANCA存在靶向关系。结论miR-214-5p可靶向降低FANCA表达抑制NB细胞增殖,参与细胞DNA损伤和化疗敏感性调控。展开更多
BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highl...BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.展开更多
Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,w...Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.展开更多
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).Howev...Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.展开更多
文摘目的探讨微小RNA-214-5p(miR-214-5p)对神经母细胞瘤(NB)DNA损伤和化疗敏感性的调控作用及机制。方法通过TARGET数据库分析范可尼贫血互补组A型(fanconi anemia complementary group A protein,FACNA)蛋白与NB临床病理特征的关系。构建miR-214-5p低表达、FANCA过/低表达NB细胞系,采用细胞计数试剂盒-8(CCK-8)、移植瘤模型检测其表达对NB体内外增殖的影响,并验证miR-214-5p与FANCA靶向关系。结果GEO数据库和TARGET数据库中筛查出与NB相关的交集基因为FANCA,其表达与调节细胞增殖基因、预后及临床病理特征密切相关(P<0.05)。与空载体(Vector)组比较,FANCA组细胞活力、移植瘤体积和重量升高(P<0.05);与shNC组比较,shFANCA1组、shFANCA2组细胞活力降低(P<0.05);与对照组比较,1 mmol/L过氧化氢(H_(2)O_(2))处理后磷酸化组蛋白γ-H2AX升高(P<0.05),但FANCA过表达后γ-H2AX降低(P<0.05)。随着多柔比星浓度增加,细胞活力降低,但FANCA组细胞活力高于Vector组(P<0.05)。miR-214-5p与FANCA存在靶向关系。结论miR-214-5p可靶向降低FANCA表达抑制NB细胞增殖,参与细胞DNA损伤和化疗敏感性调控。
文摘目的观察急性脑梗死(acute cerebral infarct,ACI)患者分化拮抗非蛋白编码RNA(differentiation antagonizes non-protein coding RNA,DANCR)、微小RNA-214-5p(micro RNA-214-5p,miR-214-5p)水平变化,并探讨其表达与患者脑梗死灶大小及临床预后的相关性。方法回顾性分析123例ACI患者资料。依据梗死灶大小,分为小梗死灶组(<5 cm3)39例、中梗死灶组(5~10 cm3)61例与大梗死灶组(>10 cm3)23例。采用美国国立卫生研究院卒中量表(national institute of health stroke scale,NIHSS)评分评价预后,将NIHSS评分<6分ACI患者归为预后良好组(84例),≥6分ACI患者归为预后不良组(39例)。同时选择同期体检的117名健康体检者为对照组。采用实时荧光定量PCR(realtime quantitative PCR,RT-qPCR)法对DANCR、miR-214-5p进行分析。应用Logistic回归方法,探讨ACI患者预后不良的相关因素。通过Pearson检验评估DANCR与miR-214-5p的相关性。本研究拟采用受试者工作特性(receiver operating characteristic,ROC)曲线,研究DANCR、miR-214-5p在ACI患者中的表达及临床意义。结果与对照组比较,ACI患者DANCR表达明显增高(P<0.001),而miR-214-5p明显下降(P<0.001)。ACI患者DANCR与miR-214-5p之间存在显著负相关(r=-0.486,P<0.001)。与小梗死灶组比较,中梗死灶组、大梗死灶组患者DANCR水平显著升高、miR-214-5p水平显著降低(均P<0.05);与中梗死灶组比较,大梗死灶组患者DANCR水平显著升高,miR-214-5p水平显著降低(均P<0.05)。与预后良好组比较,预后不良组患者血清DANCR水平更高、发病至入院时间更长,miR-214-5p水平显著降低(均P<0.001)。DANCR是影响ACI患者预后不良的危险因素(OR=2.013,95%CI:1.079~3.754,P=0.028),miR-214-5p是保护因素(OR=0.806,95%CI:0.657~0.988,P=0.038)。DANCR、miR-214-5p以及二者联合诊断ACI患者预后不良的ROC曲线下面积(area under the curve,AUC)分别为0.727、0.739和0.857,二者联合诊断效能高于单独检测效能(Z=2.070,P=0.038;Z=2.097,P=0.036)。结论ACI患者血清DANCR高表达、miR-214-5p低表达可能与其脑梗死灶大小及预后均存在重要联系,二者联合对诊断患者发生不良预后具有一定价值。
基金Supported by the National Natural Science Foundation of China,No.82274528.
文摘BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.
基金the National Natural Science Foundation of China,No.82170406 and No.81970238the Royal Society United Kingdom,No.IEC\NSFC\201094.
文摘Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.
基金supported by the National Natural Science Foundation of China(Grant No.:82225048)the Dalian Science and Technology Leading Talents Project,China(Grant No.:2019RD15)Sanming Project of Medicine in Shenzhen,China(Grant No.:SZZYSM202106004).
文摘Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
