Figure 4.

The regulatory role of circRNAs in HCC angiogenesis. VEGF protein binds with VEGFR 2 and activates the PI3K/AKT and MAPK/MEK signaling pathways, which induces HIF-1α expression. HIF-1α translocates into the nucleus and partners with HIF-1β to form a heterodimer that activates VEGF and promotes angiogenesis. Dysregulated circRNAs interfere with the expression of VEGF and HIF-1α in HCC. circRNAs with pro-angiogenic potential are denoted as red circles whereas anti-angiogenic circRNAs are denoted as green circles. HIF-1α, hypoxia-inducible factor 1α; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2.