Moreover, mutating the K108 residue of hnRNPA2B1 or SIM in ALIX significantly impaired the enrichment of circTLCD4-RWDD3 and hnRNPA2B1 in NSCLC cell-secreted EVs (Fig. 5m, n), further confirming that SUMOylated hnRNPA2B1 activates ALIX to package circTLCD4-RWDD3 and hnRNPA2B1 into NSCLC cell-secreted EVs. This evidence concerns the gene PDCD6IP and non-small cell lung carcinoma.