However, the present study shows the IL-6/STAT3/S1PR pathway appears to not be implicated in the inhibitory effect of SphK1 deficiency on liver carcinogenesis, but also many other signaling molecules such as TNF-α, IL-1α, IL-1β, TGF-β1 and HMGB1, which were reported in previous studies to play essential roles in the development of liver cancer [42–45], were not altered by SphK1 deletion. The gene discussed is HMGB1; the disease is liver cancer.