Open Access
ARTICLE
Melanoma cell line-derived exosomal miR-424-5p: a key promoter of angiogenesis through LATS2 interaction
JUNWEI DU, QIANG ZHANG, JING ZHANG, MAIERDANJIANG MAIHEMUTI, HAIYANG HE, RENBING JIANG*
Department of Bone and Soft Tissue Tumors and Melanoma, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830000, China
* Corresponding Author: RENBING JIANG. Email: 
Oncology Research https://doi.org/10.32604/or.2024.050878
Received 21 February 2024; Accepted 20 June 2024; Published online 26 August 2024
Abstract
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.
Keywords
Exosomal miR-424-5p; Large tumor suppressor kinase 2 (LATS2); Cell proliferation; Cancer progression; Therapeutic targets
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