PTEN silencing enhances neuronal proliferation and differentiation by activating PI3K/Akt/GSK3β pathway in vitro

Highlights: • PTEN had a dual effect on the neuronal cells in vitro. • PTEN knockdown significantly promoted neuronal cell proliferation and differentiation. • PTEN knockdown activated Akt/GSK3β and Wnt/β-catenin pathways in vitro. • GSK3β as a key node involved in PTEN controlling cell proliferation and differentiation in PC12 cells. • PTEN-GSK3β pathway modulated neuronal proliferation via β-catenin. The failure of neuronal proliferation and differentiation is a major obstacle for neural repair and regeneration after traumatic central nervous system (CNS) injury. PTEN acts as an intrinsic brake on the neuronal cells, but its roles and mechanism still remain to be clarified. Herein, for the first time we confirmed that PTEN had a dual effect on the neuronal cells in vitro. Firstly, we found that PTEN knockdown significantly promoted cell proliferation and differentiation. Then, PTEN knockdown activated PI3K/Akt and Wnt/β-catenin pathways in vitro. Further evidence revealed that GSK3β as a key node involved in PTEN controlling cell proliferation and differentiation in PC12 cells. In addition, we identified that PTEN-GSK3β pathway modulated neuronal proliferation via β-catenin. Taken together, these results suggest that PTEN silencing enhances neuronal proliferation and differentiation by activating PI3K/Akt/GSK3β pathway that it may be a promising therapeutic approach for CNS injury.