miR-208a-3p targets PPP6C to regulate the progression of Radiation-induced lung injury

Aims: Radiation-induced lung injury (RILI) is a common complication after radiotherapy for clinical thoracic tumors, and increasing evidence suggests that miRNAs have potential value as biomarkers for early warning. However, the potential mechanism is still obscure. Here, we evaluated miRNAs-dependent mechanism involved in response and therapy of RILI. 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 PPP6C and activating the cGAS/STING pathway. Overexpression of PPP6C can alleviate Radiation-induced DNA damage and excessive accumulation of ROS. It was also observed that PPP6C inhibited ionizing Radiation-induced pulmonary pneumonia in vivo. Innovation and Conclusion: miR-208a-3p/PPP6C represent a potential diagnostic marker and therapeutic target for Radiation-induced lung injury which needs to be verified by future clinical studies. All animal experiments were approved by the Medical Ethics Committee of the Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital (2020-13). 6-8 week-old C57BL/6 mice were divided into control group and experimental group. Mice were held under circumstances (24 ± 2 °C, 40-70% relative humidity, 12 h light/12 h dark cycle) and were given regular diet and water. Mice were irradiated using an X-RAD 225 irradiator (X-ray: 225 kV and 12.5 mA; SSD: 30 cm; beam filter: 2.0 mm AI). The mice were setted in the center of the radiance field at a dose rate of 200 cGy/min at a distance of 30 cm from the irRadiation source and the mice were immobilized in a specially designed fixture designed to irradiate the entire thoracic cavity of the mouse, A total dose of 15 Gy while avoiding exposure to other parts of the body.