Fig. 8

A schematic model visualizing the inhibitory mechanism of circPSD3 in vascular invasion and metastasis of HCC. Vascular invasion is a major route for intrahepatic and distant metastasis (lung, brain, pelvic, etc.) of HCC. circPSD3 is back-spliced by exons 13 and 14 of pre-PSD3. The biogenesis of circPSD3 is negatively regulated by TDP43. Preferential localisation of circPSD3 in the cytoplasm retains HDAC1 in the cytoplasm, thereby reducing the inhibitory effect of HDAC1 on the transcription of SERPINB2. As an endogenous inhibitor of the uPA system, SERPINB2 interacts with uPA to induce endocytosis of uPA–uPAR complexes, thus to inhibit the activation of plasminogen and attenuate the degradation of extracellular matrix and basement membrane by plasmin