SPIN1 accelerates tumorigenesis and confers radioresistance of non-small cell lung cancer via orchestrating the FOXO3a/FOXM1 axis

Radioresistance is a predominant obstacle of effective treatments in non-small cell lung cancer (NSCLC), while the underlying mechanism remains incompletely elucidated. Spindlin 1(SPIN1) has been reported to participate in tumor initiation and progression, while its role in NSCLC tumorigenesis and radioresistance remains largely unknown. In this study, bioinformatics analysis, immunohistochemistry (IHC) and western blotting assays were performed to test SPIN1 expression in NSCLC samples and cell lines. The carcinogenic role of SPIN1 was evaluated by cell growth and proliferation, EdU staining, transwell and colony formation assays. Besides, the radiosensitivity of NSCLC cells was determined by clonogenic cell survival, neutral comet and γ-H2AX and Rad51 foci formation assays. Xenograft tumor model was constructed to access the effects of SPIN1 on tumorigenesis and radiosensitivity. Furthermore, RNA sequencing, quantitative real-time PCR, CHX and ubiquitination assays were applied to elucidate the correlation between SPIN1 and FOXO3a-FOXM1 axis. Therefore, our results suggest that the SPIN1-MDM2-FOXO3a/FOXM1 signaling axis is essential for NSCLC progression and radioresistance, and it could serve as therapeutic targets in irradiation-resistance NSCLC.