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.
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