LncRNA CPS1-IT1 attenuates radiation resistance by inhibiting MAPK7 expression via stabling stromal cell-derived miR-125b-5p in non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is one of the most common malignances, and NSCLC survival rates remain low. Radiation therapy is the established definitive option except surgery for early-stage NSCLC, the therapeutic effectiveness is poor due to radiation resistance. The mechanisms of how radiation-resistant NSCLC cells are protected from radiation are unclear. This study aims to investigate how non-coding RNAs affect signaling pathways to confer protection against radiation treatment in radiation-resistant NSCLC cells. Here, NSCLC cells stably expressing the long non-coding RNA (lncRNA) carbamoyl-phosphate synthetase 1 intronic transcript 1 (CPS1-IT1) or microRNA (miRNA) miR-125 b-5p were established. Besides, chromatin isolation by RNA purification (ChIRP) was used to identify lncRNA-DNA interactions. Moreover, RNA-protein interactions were detected by RNA antisense purification (RAP). This study indicates that CPS1-IT1 or miR-125 b-5p over-expression sensitize radiation-resistant NSCLC cells to radiation treatment both in vitro and in vivo . Mechanistically, CPS1-IT1 suppresses mitogen-activated protein kinase 7 (MAPK7) transcription through interacting with EZH2 and NOP58 to enhance histone methylation at the MAPK7 gene promoter. Moreover, CPS1-IT1-stabilized miR-125 b-5p derived from stromal cells in NSCLC cells also attenuates radiation resistance by TRAF6-EZH2-MAPK7 pathway. Together, these findings indicate that CPS1-IT1 attenuates the radiation resistance through repressing MAPK7 expression by NOP58/EZH2 axis via stabling stromal cell-derived miR-125 b-5p in NSCLC, warranting further preclinical evaluation as candidate strategies for modulating NSCLC radiation response.