In addition, mutating the K108 SUMOylation modification site of hnRNPA2B1 or SIM in ALIX significantly inhibited the activation of ALIX and suppressed the biological capacity of ALIX to recruit ESCRT-III component, thereby impairing the enrichment of circTLCD4-RWDD3 in NSCLC cell-derived EVs. The gene discussed is SIM2; the disease is non-small cell lung carcinoma.