As shown in Supplementary Fig. 6h, i, the volume of popliteal LNs and popliteal LN metastasis rate were significantly increased in mice injected with circTLCD4-RWDD3-overexpressing NSCLC cell-derived EVs compared with the control group, whereas inhibiting the SUMO2 modification on hnRNPA2B1 by mutating K108 residue of hnRNPA2B1 attenuated this effect, indicating that SUMOylated hnRNPA2B1-mediated package of circTLCD4-RWDD3 into NSCLC cells-derived EVs is essential for the LN metastasis of NSCLC in vivo. Here, HNRNPA2B1 is linked to non-small cell lung carcinoma.