Exosome-mediated miR-4655-3p contributes to UV radiation-induced bystander effects

Radiation-induced bystander effects (RIBEs) refer to a series of reactions displaying in nonirradiated cells triggered by signals from irradiated cells. Though bystander effects induced by ionizing radiation have been well studied, there are still limited data on ultraviolet(UV) induced bystander effects(UV-RIBEs). Studies have verified that exosomes, acting as a new tool of intercellular communication, participate in ionizing radiation-induced bystander effect. The purpose of what we studied was to explore the function of exosomes in UV-RIBEs, and seeking the relevant mechanism. Human skin fibroblasts (HSFs) were exposed to a single dose of ultraviolet A (UVA) radiation (20 J/cm²) or ultraviolet B (UVB) radiation (60 mJ/cm²), respectively. Exosomes were isolated from the culture medium of HSFs by differential ultracentrifugation. Three endpoints relevant to potodamage were used in the evaluation of UV-RIBEs, which including the cell proliferation, oxidative damage, and apoptosis. Our results showed that exosomes from UV-irradiated cells contributed to UV-RIBEs. The expression of miR-4655-3p in exosomes increased after UV radiation and exosomes assisted in the transportation of miR-4655-3p between cells. The upregulation of miR-4655-3p enhanced the UV-RIBEs in the bystander cells. MiR-4655-3p restrained the expression of E2F2 through direct binding to its 3'-UTR. In addition, E2F2 contributed to the cell proliferation and decreased oxidative damage of HSFs. To sum up that exosomal miR-4655-3p plays a crucial role in UV-RIBEs and this function mentioned partially related to the inhibition of E2F2.