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

<b><i>Aims:</i></b> 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. <b><i>Results:</i></b> Our data showed that mmu-miR-208a-3p was consistently highly expressed in the lung tissue of irradiated mice. <i>In vitro</i> 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 <i>in vivo</i>. <b><i>Innovation and Conclusion:</i></b> miR-208a-3p/PPP6C represents a potential therapeutic target for RP which needs to be verified by future clinical studies. <i>Antioxid. Redox Signal.</i> 43, 239-253.