Moreover, mutating ALIX SIM or downregulating CHMP4B greatly impaired the expression levels of circTLCD4-RWDD3 and SUMOylated hnRNPA2B1 in EVs (Fig. 5q, r, Supplementary Fig. 4y), indicating that SUMOylated hnRNPA2B1 activates ALIX to recruit ESCRT-III and facilitate the sorting of circTLCD4-RWDD3 and SUMOylated hnRNPA2B1 into NSCLC cell-derived EVs. This evidence concerns the gene CHMP4B and non-small cell lung carcinoma.