Objectives:Melanoma is a highly aggressive and metastatic form of cancer,and the role of exosomal microRNAs(miRNAs)in its progression remains largely unexplored.This study aimed to investigate the effects of melanoma ...Objectives:Melanoma is a highly aggressive and metastatic form of cancer,and the role of exosomal microRNAs(miRNAs)in its progression remains largely unexplored.This study aimed to investigate the effects of melanoma cell-derived exosomal miR-424-5p on angiogenesis and its underlying mechanisms.Methods:Exosomes were isolated from melanoma cell lines A375 and A2058,and their effects on the proliferation,migration,and angiogenesis of human umbilical vein endothelial cells(HUVECs)were examined.The interaction between miR-424-5p and its target gene,large tumor suppressor kinase 2(LATS2),was analyzed using luciferase reporter assays and functional experiments.In vivo,tumor growth and angiogenesis were studied in a xenograft model using nude mice.Results:Melanoma cell-derived exosomes could be internalized by HUVECs,which promoted proliferation,migration,and angiogenesis.miR-424-5p was highly expressed in melanoma cells and their exosomes,and its inhibition in exosomes suppressed HUVEC proliferation,migration,and angiogenesis.LATS2 was identified as a direct target of miR-424-5p,and its silencing reversed the inhibitory effects of miR-424-5p inhibition on HUVEC functions.In vivo,exosomes derived from miR-424-5p-inhibited melanoma cells suppressed tumor growth and angiogenesis in xenograft models.Conclusions:Melanoma cell-derived exosomal miR-424-5p promotes angiogenesis by targeting LATS2,contributing to melanoma progression.Targeting the exosomal miR-424-5p/LATS2 axis could be a potential therapeutic strategy for melanoma.展开更多
目的检测新生儿缺氧缺血性脑病(HIE)患儿血清中miR-15b、miR-424表达水平,探讨二者与HIE发生发展和预后的关系。方法选取2015年4月—2017年4月我院儿科收治的68例HIE患儿为试验组,根据患儿临床HIE分度标准分为轻度组、中度组和重度组;...目的检测新生儿缺氧缺血性脑病(HIE)患儿血清中miR-15b、miR-424表达水平,探讨二者与HIE发生发展和预后的关系。方法选取2015年4月—2017年4月我院儿科收治的68例HIE患儿为试验组,根据患儿临床HIE分度标准分为轻度组、中度组和重度组;另选取68名在本院同期分娩的正常足月健康婴儿为对照组。收集两组临床资料,采用实时荧光定量PCR(qRT-PCR)法检测HIE患儿和健康新生儿血清中miR-15b、miR-424表达水平;分析HIE患儿血清miR-15b、miR-424水平与各生化指标的相关性。出生后28 d测定新生儿神经行为量表(NBNA)评分,评估新生儿神经行为,分析miR-15b、miR-424表达水平与HIE患儿NBNA评分、预后的关系。结果HIE患儿血清miR-15b、miR-424表达水平均低于健康婴儿(P<0.05);重度组、中度组HIE患儿血清miR-15b、miR-424表达水平均低于轻度组(P<0.05),重度组HIE患儿血清miR-15b、miR-424表达水平均低于中度组(P<0.05)。重度组、中度组HIE患儿出生后28 d NBNA评分低于轻度组(P<0.05),重度组HIE患儿出生后28 d NBNA评分低于中度组(P<0.05)。相关性分析显示,血清miR-15b、miR-424表达水平与HIE患儿出生后28 d NBNA评分均呈正相关(P<0.05);预后良好的HIE患儿血清miR-15b、miR-424高表达率均明显高于预后不良的患儿(P<0.05)。结论HIE患儿血清miR-15b、miR-424表达水平均明显下调,与HIE临床分度、出生后28 d NBNA评分有关,且可影响患儿的预后。展开更多
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01C803).
文摘Objectives:Melanoma is a highly aggressive and metastatic form of cancer,and the role of exosomal microRNAs(miRNAs)in its progression remains largely unexplored.This study aimed to investigate the effects of melanoma cell-derived exosomal miR-424-5p on angiogenesis and its underlying mechanisms.Methods:Exosomes were isolated from melanoma cell lines A375 and A2058,and their effects on the proliferation,migration,and angiogenesis of human umbilical vein endothelial cells(HUVECs)were examined.The interaction between miR-424-5p and its target gene,large tumor suppressor kinase 2(LATS2),was analyzed using luciferase reporter assays and functional experiments.In vivo,tumor growth and angiogenesis were studied in a xenograft model using nude mice.Results:Melanoma cell-derived exosomes could be internalized by HUVECs,which promoted proliferation,migration,and angiogenesis.miR-424-5p was highly expressed in melanoma cells and their exosomes,and its inhibition in exosomes suppressed HUVEC proliferation,migration,and angiogenesis.LATS2 was identified as a direct target of miR-424-5p,and its silencing reversed the inhibitory effects of miR-424-5p inhibition on HUVEC functions.In vivo,exosomes derived from miR-424-5p-inhibited melanoma cells suppressed tumor growth and angiogenesis in xenograft models.Conclusions:Melanoma cell-derived exosomal miR-424-5p promotes angiogenesis by targeting LATS2,contributing to melanoma progression.Targeting the exosomal miR-424-5p/LATS2 axis could be a potential therapeutic strategy for melanoma.
文摘目的检测新生儿缺氧缺血性脑病(HIE)患儿血清中miR-15b、miR-424表达水平,探讨二者与HIE发生发展和预后的关系。方法选取2015年4月—2017年4月我院儿科收治的68例HIE患儿为试验组,根据患儿临床HIE分度标准分为轻度组、中度组和重度组;另选取68名在本院同期分娩的正常足月健康婴儿为对照组。收集两组临床资料,采用实时荧光定量PCR(qRT-PCR)法检测HIE患儿和健康新生儿血清中miR-15b、miR-424表达水平;分析HIE患儿血清miR-15b、miR-424水平与各生化指标的相关性。出生后28 d测定新生儿神经行为量表(NBNA)评分,评估新生儿神经行为,分析miR-15b、miR-424表达水平与HIE患儿NBNA评分、预后的关系。结果HIE患儿血清miR-15b、miR-424表达水平均低于健康婴儿(P<0.05);重度组、中度组HIE患儿血清miR-15b、miR-424表达水平均低于轻度组(P<0.05),重度组HIE患儿血清miR-15b、miR-424表达水平均低于中度组(P<0.05)。重度组、中度组HIE患儿出生后28 d NBNA评分低于轻度组(P<0.05),重度组HIE患儿出生后28 d NBNA评分低于中度组(P<0.05)。相关性分析显示,血清miR-15b、miR-424表达水平与HIE患儿出生后28 d NBNA评分均呈正相关(P<0.05);预后良好的HIE患儿血清miR-15b、miR-424高表达率均明显高于预后不良的患儿(P<0.05)。结论HIE患儿血清miR-15b、miR-424表达水平均明显下调,与HIE临床分度、出生后28 d NBNA评分有关,且可影响患儿的预后。
