The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

摘要: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but underlying molecular mechanisms for better understanding this phenomenon caused intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 unirradiated cells RIBEs, direct evidence hypothesis that RIBE epigenetically regulated limited how mediates RIBEs unknown. Reactive oxygen species (ROS) have been to be involved however, roles anti-oxidative stress system unclear. Using transwell insert co-culture system, we investigated medium-mediated responses WS1 human fibroblasts after with HaCaT keratinocytes traversed α-particles. Results showed ROS levels were significantly elevated 30min co-culture, 53BP1 foci, a surrogate marker DNA damage, obviously induced 3h co-culture. This indicates occurrence oxidative damage irradiated keratinocytes. Furthermore, expression was increased cells, downregulation eliminated responses, overexpression alone could induce bystander-like cells. These data indicate mediating RIBEs. In addition, MnSOD or SOD2 effects, abolished indicating critical induction Moreover, found SOD2, suggesting might mediate through its regulation on SOD2. conclusion, revealed profound miR-21-regulated effects α-irradiated