Delivery of miR-224-5p by Exosomes from Cancer-Associated Fibroblasts Potentiates Progression of Clear Cell Renal Cell Carcinoma

Objectives. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Cancer-associated fibroblasts (CAFs) as the primary components of cancer stroma can affect tumor progression by secreting exosomes, while exosomes are carriers for proteins, nucleic acids, and other agents that responsible for delivery of biological information. Given this, exosomes derived from CAFs are emerging as promising biomarkers in clinical cancer diagnosis. Nevertheless, their role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. Methods. Here, we separated fibroblasts from ccRCC tissue, extracted exosomes, observed their morphology, and detected the expression of exosome marker proteins including Hsp70, CD9, and CD63. In the meantime, we labeled exosomes and performed coculture experiment to verify the delivery of miR-224-5p from CAFs to 769-P cells with exosomes as a carrier, so as to clarify the effect of CAF-derived exosomes on ccRCC cell malignant behaviors, as well as to discuss how miR-224-5p involves in above regulation. Results. Transmission electron microscopy was firstly applied, and it was noted that the exosomes we isolated were in normal range. Besides, Western blot also confirmed the presence of exosome marker proteins Hsp70, CD9, and CD63. Furthermore, coculture experiments were performed and the CAF-derived exosomes were observed to be able to facilitate the malignant behaviors of ccRCC cells, and the exosomal miR-224-5p could be internalized by ccRCC cells to participate in regulation of cell proliferation, migration, invasion, and apoptosis. Conclusion. To sum up, miR-224-5p can enter ccRCC cells via CAF-derived exosomes, in turn, promoting the malignant behaviors of ccRCC cells, which indicates that miR-224-5p has the potential severing as a therapeutic target for ccRCC.

Automated summary

The study revealed that exosomes derived from CAFs can impact the malignant behaviors of ccRCC cells, particularly through the involvement of miR-224-5p. MiR-224-5p can enter ccRCC cells through exosomes and promote their malignant behaviors.