In addition, and as previously reported,36 we observed that RUNX2 suppression results in a strong downregulation of NUPR1 and of the NUPR1-regulated genes RELB and IER3. These data imply the existence of a NUPR1/RELB/IER3/RUNX2 pathway that may act as an auto-regulatory loop, which we demonstrated as having a key role in HCC cell growth, migration, invasion and chemoresistance. This evidence concerns the gene NUPR1 and hepatocellular carcinoma.