摘要：SummaryReversing chemotherapy resistance in small cell lung cancer (SCLC) is crucial to improve patient prognosis. The present study aims to investigate the underlying mechanisms in SCLC chemoresistance. We see that nuclear receptor binding factor 2 (NRBF2) is a poor prognostic factor in SCLC. The effects of NRBF2 on chemoresistance were determined in SCLC. The underlying molecular mechanisms of NRBF2 in the autophagy process in SCLC were examined. NRBF2 positively regulated autophagy, leading to drug resistance in SCLC. The MIT domain of NRBF2 directly interacted with the PB1 domain of P62. This interaction increased autophagic P62 body formation, revealing the regulatory role of NRBF2 in autophagy. Notably, NRBF2 was directly modulated by the transcription factor XRCC6. The MIT domain of NRBF2 interacts with the PB1 domain of P62 to regulate the autophagy process, resulting in SCLC chemoresistance. NRBF2 is likely a useful chemotherapy response marker and therapeutic target in SCLC.Graphical abstractDisplay OmittedHighlights•NRBF2 promoted the chemoresistance of SCLCin vitroandin vivo•The chemoresistance induced by NRBF2 was mediated via autophagy in SCLC•NRBF2 interacting with P62 contributed to autophagic P62 bodies' formation•NRBF2 was regulated by XRCC6 via direct binding to the NRBF2 gene promoterCell biology; Cancer
