Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4

Journal of Experimental & Clinical Cancer Research

Haolan Xi¹  Wenkang Luan²  Shaojun Ma²  Hongru Ruan²  Jinlong Wang²  Feng Lu²  Yuting Ding³ 

[1] Department of Ophthalmology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China;Department of Plastic Surgery, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Road, 212000, Zhenjiang, Jiangsu, China;Department of Rehabilitation, Changshu No. 2 People’s Hospital (The 5th Clinical Medical College of Yangzhou University), Changshu, Jiangsu, China;

关键词: Melanoma;    Exosomal;    miR-106b-5p;    EphA4;    EMT;   

DOI  :  10.1186/s13046-021-01906-w

来源: Springer

【 摘 要 】

BackgroundCancer-secreted exosomal miRNAs regulates the biological processes of many tumours. The serum level of exosomal miR-106b-5p is significantly increased in melanoma patients. However, the role and molecular mechanisms of exosomal miR-106b-5p in melanoma remains unclear.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-106b-5p and EphA4 in melanoma tissues. Transmission electron microscopy (TEM) and western blotting were used to identify exosome. QRT-qPCR and Cy3-labelled miR-106b-5p were used to demonstrated the transmission of melanoma cell-secreted exosomal miR-106b-5p. Western blotting, Immunofluorescence, adhesion, transwell and scratch wound assay were used to explore the role of exosomal miR-106b-5p in melanocytes. Luciferase reporter assays and RNA-Chromatin Immunoprecipitation (ChIP) assay were used to confirm whether erythropoietin-producing hepatocellular carcinoma receptor A4 (EphA4) was a direct target of miR-106b-5p.ResultsWe found that miR-106b-5p levels were increased in melanoma tissue, and high miR-106b-5p expression is an independent risk factor for the overall survival of patients with melanoma. miR-106b-5p is enriched in melanoma cell-secreted exosomes and transferred to melanocytes. Exosomal miR-106b-5p promotes the epithelial-to-mesenchymal transition (EMT), migration, invasion and adhesion of melanocytes. Exosomal miR-106b-5p exerted its role by targeting EphA4 to activate the ERK pathway. We demonstrated that exosomal miR-106b-5p promoted melanoma metastasis in vivo through pulmonary metastasis assay.ConclusionsThus, melanoma cell-secreted exosomal miR-106b-5p may serve as a diagnostic indicator and potential therapeutic target in melanoma patients.

【 授权许可】

CC BY