Targeting FBXO22 enhances radiosensitivity of non-small cell lung cancer by inhibiting FOXM1/Rad51 axis

FBXO22 is the substrate recognition subunit of SCF E3 ubiquitin ligase, which plays an important role in the occurrence, development and therapeutic response of solid tumors.At present, the relationship between FBXO22 and radiosensitivity of lung cancer has not been fully elucidated.Here we present evidence to prove that abnormally expressed FBXO22 in lung cancer promotes transcriptional activation of homologous recombination enzyme Rad51 by up-regulating transcription factor FOXM1, which in turn induces radioresistance in lung cancer.By comparing with the reference data set of cMap database, Deguelin was identified as a small molecular inhibitor of FBXO22.Deguelin increases the radiosensitivity of lung cancer cells in vitro and in vivo in a FBXO22-dependent manner and is safely tolerated.This study revealed the identity of a novel radioresistance biomarker of FBXO22 and provided preclinical evidence for the clinical transformation of this target by screening small molecular inhibitors. A549 cells transfected with Scrambled or SiRNAs targeting FBXO22 for 48 hours were analyzed by RNA-seq.