Figure 2. The downregulation of circular RNAs promotes lung cancer progression through the upregulation of the Wnt/β-catenin pathway. A, B, reduced levels of circ-ITCH and circ-0043256 promotes aggregation of miR-7/miR-214 and miR-7/miR-1252 respectively, which causes ITCH reduction. Increased DVL as a result of ITCH downregulation, stabilizes β-catenin in cells and induces the Wnt/β-catenin pathway. C, inhibitory effect on miR-378 declines, by downregulation of circ-0007059 which causes ERK1/2 rise. ERK1/2 activates the Wnt/β-catenin pathway by interaction with the LRP protein. D, E, a drop of circ-0006427 and circ-18414 expression in lung cancer cells, results in upregulation of miR-6783-3P and miR-6807-3P respectively, which depletes DKK1 expression and Wnt/β-catenin pathway activation. Abbreviations: ITCH, Itchy E3 Ubiquitin Protein Ligase; LRP, Low-density lipoprotein receptor-related protein; DVL, Dishevelled; ERK1/2, extracellular signal-regulated kinases 1/2; DKK1, dickkopf1.