For example, angiopoietin-like protein (ANGPTL1) acts as a tumor suppressor, not only inhibiting STAT3/Bcl-2–driven anti-apoptotic signals to promote apoptosis but also downregulating certain transcription factors (e.g., SNAIL and SLUG) to suppress cell migration and invasion.270–272 Many studies have revealed that DNA hypermethylation in promotors can be associated with tumor suppressor gene dysfunction, leading to HCC development and progression.273,274 Thus, the downregulation of ANGPTL1 is insufficient to inhibit STAT3 signaling.275. This evidence concerns the gene STAT3 and hepatocellular carcinoma.