We simultaneously analyzed the RNA-seq results of TRIM15 and the sequencing results of TKI resistant cells and found that there were three genes, PGF, GNG4, THBS4, associated with the PI3K-AKT signaling pathway were changed after TRIM15 depletion or in regorafenib resistant HCC cells (Supplementary Fig. 4b). The gene discussed is AKT1; the disease is hepatocellular carcinoma.