TRDMT1 methyltransferase gene knockout attenuates STING-based cell death signaling during self-extracellular RNA-mediated response in drug-induced senescent osteosarcoma cells. (PubMed, Cell Mol Life Sci)
In the present study, self-extracellular RNA was obtained from dying (RNA D) and senescent (RNA S) cellular models of osteosarcoma (OS), characterized by NGS, and tested against proliferating and non-proliferating (etoposide-indued senescent) OS cells (U-2 OS, SaOS-2, MG-63, 143B)...TRDMT1 KO also resulted in replication stress in OS cells that was potentiated by RNA D and RNA S stimulation and associated with elevated levels of APOBEC3A and APOBEC3G, members of the cytidine deaminase protein family. In conclusion, we showed that TRDMT1 KO restricted STING-based immune and cell death response to RNA D and RNA S in non-proliferating drug resistant OS cells that might have potential therapeutic implications.