Its dual effects include: on one hand, inhibiting SphK1 downregulates NF-κB p65 activity and modulates ceramide levels [e.g., with DMS intervention (31)], inducing tumor cell apoptosis; on the other hand, SphK1 activates Rho GTPases and matrix metalloproteinases (MMPs), promoting epithelial-mesenchymal transition (EMT), thereby enhancing HCC cell invasion and distant metastasis (32). This evidence concerns the gene NFKB1 and hepatocellular carcinoma.