Red Blood Cell-Derived Exosomal Oncogenic MicroRNA Promote Cancer Development and Progression.

The role of red blood cells (RBCs) in tumorigenesis is poorly understood. We previously identified RBC-microRNAs with aberrations linked to lung cancer, including miR-93-5p. Here we find that miR-93-5p levels are elevated in RBC-derived exosomes among lung cancer patients and are associated with their shorter survivals. RBC-derived miR-93-5p transfers to cancer cells primarily through the exosomal pathway. The transferred RBC-miR-93-5p can target PTEN in cancer cells, and hence increase cell proliferation, invasion, and migration. RBC-derived miR-93-5p accelerates, whereas targeting miR-93-5p diminishes tumor growth in xenograft models. These findings reveal a novel biological function of RBCs in tumorigenesis, where they facilitate cancer progression by transferring the oncomiR via exosomes, thereby offering new diagnostic and treatment strategies for lung cancer.