TLCD4 and non-small cell lung carcinoma: Additionally, we successfully established circTLCD4-RWDD3-knockout (circTLCD4-RWDD3KO) NSCLC cell lines by transfecting paired gRNAs targeting the boundaries of the Alu sequence in the intron upstream of TLCD4-RWDD3 exon 2 (Supplementary Fig. 2h, i), thereby deleting the critical Alu element and demonstrated that EVs derived from circTLCD4-RWDD3KO A549 and H1299 cells markedly suppressed the tube formation and migration of HLECs compared with the control group (Supplementary Fig. 2j–m).