Subsequently, biological functional experiments were devised to uncover significantly weakened cell viability (all p < 0.001) (Fig. 5B), migration (ACHN: q = 16.036, p < 0.001; 769-P: q = 13.803, p < 0.001) (Fig. 5C, Fig. S2E) and invasion (ACHN: q = 14.363, p < 0.001; 769-P: q = 10.106, p < 0.001) (Fig. 5D, Fig. S2F) in oe-NEDD4L group vs. oe-NC group, while profoundly enhanced abilities of RCC cells after M2-EVs application when compared with oe-NEDD4L alone (all p < 0.001) (Figs. 5B–5D, Figs. S2E, S2F). The gene discussed is NEDD4L; the disease is renal cell carcinoma.