Affiliations: [a] Department of Dermatology, Shigatse People’s Hospital, Shigatse, The Tibet Autonomous Region, China | [b] Department of Medical and Political Science, Shigatse People’s Hospital, Shigatse, The Tibet Autonomous Region, China | [c] Department of Gastric Cancer Sugery, Fudan University Shanghai Cancer Center, Shanghai, China | [d] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Correspondence:
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Corresponding author: Ziwen Long, Department of Gastric Cancer Sugery, Fudan University Shanghai Cancer Center, Building 3, No. 270, Dongan Road, Xuhui District, Shanghai 200032, China. Tel.: +86 54237417; E-mail: longzw@shmu.edu.cn.
Note: [1] Co-first author.
Abstract: Melanoma, a skin cancer derived from malignant melanocytes, is characterized by high aggressiveness and mortality. However, its exact etiology is unknown. Recently, the roles of exosomes and exosomal microRNAs (miRNAs) in the progression and therapy of various disorders, including melanoma, have gained attention. We investigated the impact of miR-138-5p from exosomes released by human mesenchymal stem cells (HMSCs) on the pathogenesis of melanoma. We isolated exosomes from HMSCs (HMSC-exos) by ultracentrifugation and verified them by specific biomarkers and transmission electron microscopy. We used CCK8, flow cytometry, quantitative real-time PCR (qRT-PCR), and Western blots to investigate cell proliferation, apoptosis, and mRNA and protein levels, respectively. Additionally, we used luciferase assays to examine the relationship between miR-138-5p and SOX4. Administration of HMSC-exos dramatically repressed the growth of melanoma cells. Elevated miR-138-5p levels in HMSC-exos were linked to increased cell apoptosis, and miR-138-5p downregulation had the opposite effects on cells. SOX4 was targeted by miR-138-5p through direct binding to the SOX4 3’UTR. In melanoma tissues, miR-138-5p was downregulated, and SOX4 was upregulated and was negatively correlated. MiR-138-5p plays a crucial role in melanoma progression. The negative regulation of SOX4 transcription mediates the function of miR-138-5p. These findings provide a novel concept of melanoma pathogenesis and identify a valuable target (miR-138-5p/SOX4 axis) in treating this disease.
