Circ-Smad5 Retards the G1/S Transition of Cell Cycle by Inhibiting the Activity of Wnt/Lef/Cyclin D1 Signaling in JB6 Cells

The study investigated the role of circ-Smad5 in JB6 cells, revealing that circ-Smad5 inhibited cell proliferation and cell cycle progression by suppressing the Wnt/β-catenin/Lef 1 signaling pathway, which in turn reduced cyclin D1 expression. Lentivirus vectors were used to manipulate circ-Smad5 levels, and various assays confirmed that lower circ-Smad5 expression led to increased S phase cells and cyclin D1 protein levels. These effects were reversible with the Wnt signaling inhibitor PNU-74654. This research was the first to report the function of circ-Smad5, suggesting its potential role in regulating cell proliferation through Wnt signaling inhibition.