Figure 6.

Proposed model for the function of miR-663 in TGF-β1-mediated RIBE. In irradiated cells, miR-663 downregulation leads to derepression of the TGFB1 transcript, partially resulting in increased TGF-β1 protein levels in the culture medium. TGF-β1 in culture medium diffuses to bystander cells to trigger intracellular signaling, including induction of DNA damage. In bystander cells, miR-663 is upregulated via TGF-β1 signaling, and in turn, inhibits expression of TGF-β1, resulting in lower TGF-β1 production and secretion. Thus, bystander effects are observed in a distance-dependent manner.