期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 40, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13046-021-01906-w
关键词
Melanoma; Exosomal; miR-106b-5p; EphA4; EMT
类别
资金
- National Natural Science Foundation of China [81802726]
- Zhenjiang Social Development Foundation of Zhenjiang key RD projects [SH2020044]
This study revealed that miR-106b-5p levels are elevated in melanoma tissues, and high expression of miR-106b-5p is an independent risk factor for overall survival in melanoma patients. Exosomal miR-106b-5p promotes melanocyte migration, invasion and metastasis by targeting EphA4 to activate the ERK pathway.Overall, melanoma cell-secreted exosomal miR-106b-5p could potentially serve as a diagnostic indicator and therapeutic target for melanoma patients.
Background Cancer-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. Methods Quantitative 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. Results We 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. Conclusions Thus, melanoma cell-secreted exosomal miR-106b-5p may serve as a diagnostic indicator and potential therapeutic target in melanoma patients.
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