miR-208a-3p Targets PPP6C to Regulate the Progression of Radiation-Induced Pneumonia

Aims: Radiation-induced pneumonia (RP) is a common complication after radiotherapy for clinical thoracic tumors, and increasing evidence suggests that miRNAs have potential value in regulating radiation-induced lung injury. However, the potential mechanism is still obscure. Here, we evaluated the miRNAs-dependent mechanism involved in the progression of RP. Results: Our data showed that mmu-miR-208a-3p was consistently highly expressed in the lung tissue of irradiated mice. In vitro studies demonstrated that the expression of miR-208a-3p in cells was significantly increased after X-ray irradiation. Further mechanism studies indicated that radiation-induced upregulation of miR-208a-3p promoted inflammatory responses by suppressing the expression of protein phosphatase 6C (PPP6C) and activating the cyclic GMP-AMP synthase/stimulator of interferon genes protein pathway. Overexpression of PPP6C can alleviate radiation-induced DNA damage and excessive accumulation of ROS. It was also observed that PPP6C inhibited ionizing RP in vivo. Innovation and Conclusion: miR-208a-3p/PPP6C represents a potential therapeutic target for RP which needs to be verified by future clinical studies. Antioxid. Redox Signal. 43, 239-253.