Figure 3.

Influence of sponging circRNA on mRNA translation. (A) Overexpression of circRNAs leads to increased sequestration of miRs (red lines). Resultant diminished free miR de-represses mRNA translation. This may lead to overexpression of genes that participate in pathways involving oncogenesis. An example is overexpression of the Wnt/β-catenin pathway that results from circ-DENND4C overexpression and sponging of miR-195-5p.⁶⁷ (B) Lowered concentrations of circRNA diminish miR sponging. Increased concentrations of free miRs are available to bind to mRNA cognates, which in turn leads to inhibition of translation that is mediated by the RNA-Induced Silencing Complex (RISC). Hepatocarcinogenesis may be promoted if expression of a tumor suppressor gene is inhibited by this mechanism. An example is the effect of circMTO1 on miR-181b-5p, which leads to diminished expression of Phosphatase and Tensin homolog (PTEN) and promotes fibrosis in premalignant hepatic tissue.¹¹⁶