The relative expression level of HULC, as determined by qPCR, was about 8-fold higher in HCC samples than in normal liver tissue. Depletion of IGF2BP1 led to an increased HULC half-life and higher steady-state expression levels, indicating a post-transcriptional regulatory mechanism. Importantly, HULC represents the first IGF2BP substrate that is destabilized. To elucidate the mechanism by which IGF2BP1 destabilizes HULC, the CNOT1 protein was identified as a novel interaction partner of IGF2BP1. CNOT1 is the scaffold of the human CCR4-NOT deadenylase complex, a major component of the cytoplasmic RNA decay machinery.