Since the SIM in ALIX plays a pivotal role in binding with SUMOylated hnRNPA2B1 to further mediate packaging circTLCD4-RWDD3 into EVs and trigger the LN metastasis of NSCLC, we further sought to examine whether mutating ALIX SIM could suppress NSCLC lymphangiogenesis and LN metastasis facilitated by EV-packaged circTLCD4-RWDD3. This evidence concerns the gene HNRNPA2B1 and non-small cell lung carcinoma.