Melanoma cell line-derived exosomal miR-424-5p:a key promoter of angiogenesis through LATS2 interaction  

作　　者：JUNWEI DU QIANG ZHANG JING ZHANG MAIERDANJIANG MAIHEMUTI HAIYANG HE RENBING JIANG 

机构地区：[1]Department of Bone and Soft Tissue Tumors and Melanoma,Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi,830000,China

出　　处：《Oncology Research》2025年第2期357-367,共11页肿瘤学研究(英文)

基　　金：Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01C803).

摘　　要：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.

关 键 词：Exosomal miR-424-5p Large tumor suppressor kinase 2(LATS2) Cell proliferation Cancer progression Therapeutic targets 

分 类 号：R73[医药卫生—肿瘤]