| Institution: | 1. Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, Hunan, China;2. Department of Pathology of Xiangya Hospital and School of Basic Medical Science, Central South University, Changsha, Hunan, China;3. Department of Head and Neck Surgery, Hunan Province Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
Department of Oncology Plastic Surgery, Hunan Province Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;4. Cancer Research Institute, Central South University, Changsha, Hunan, China;5. Department of Dermatology of Xiangya Hospital, Central South University, Changsha, Hunan, China;6. Medicine School of Medicine, Tulane University Health Science Center, New Orleans, Louisiana;7. Surgical Bioengineering Laboratory, Department of Surgery, UC Davis School of Medicine, Sacramento, California;8. Department of Oncology of Third Xiangya Hospital, Central South University, Changsha, Hunan, China;9. Department of Plastic Surgery, Second Hospital of Shantou University, Shantou, Guangzhou, China |
| Abstract: | There is emerging evidence of bioactive material transport by exosomes in melanoma. However, the functions of exosome content underlying such cancer progression remain largely unknown. We aimed at determining whether exosome secretion contributes to cellular microRNA-494 (miR-494) loss and investigated the roles of miR-494 in melanoma progression. The exosomes from blood serum and cell culture conditioned media were separated by ultracentrifugation. A short hairpin RNA was used to silence rab27a for inhibiting exosome release. To address the functional role of exosomal miR-494, we assessed cell proliferation, migration, invasion capabilities, and cell apoptosis. Finally, subcutaneous xenograft and lung-metastasis models were constructed to determine the effect of exosomal miR-494 in vivo. Based on long noncoding RNA microarray analysis of melanocyte and melanoma-derived exosomes from the Gene Expression Omnibus database, we discovered that miR-494 was enriched in melanoma-derived exosomes. And miR-494 was increased in exosomes secreted from melanoma patients’ serum and A375 cells. Rab27a depletion reduced exosome secretion and rescued the abundance of cellular miR-494. Functional studies revealed that knockdown of rab27a and subsequent accumulation of miR-494 significantly suppressed the malignant phenotypes of melanoma cells via inducing cell apoptosis. Nude mice experiments confirmed that tumor growth and metastasis were suppressed by increasing miR-494 accumulation after rab27a depletion. In conclusion, blocking transferred exosome-shuttled miR-494 is a potential therapeutic option for melanoma. |
