The inhibition of miR-214 reduces the proliferation of gastric cancer cells via upregulation of GSK-3β and suppression of Wnt/β-catenin signal pathway, which provides fundamental support for the future therapy of gastric cancer.
Taken together, we suggest that high glucose and elevated O-GlcNAcylation stabilize FOXM1 protein by its reduced degradation via GSK-3β inactivation in MKN45 cells, suggesting that the higher risk of gastric cancer in diabetic patients could be partially due to O-GlcNAcylation-mediated FOXM1 stabilization.
Silencing of CUL4B also resulted in decreased Wnt and β‑catenin expression, but increased expression of GSK‑3β, caspase‑3 and cyclin E. These results indirectly demonstrate that CUL4B enhances the proliferation and invasion abilities of gastric cancer cells by upregulating the constituent factors Wnt and β‑catenin, as well as by negatively regulating the mRNA and protein expression of GSK‑3β, caspase‑3 and cyclin E. The potential mechanism of CUL4B highlighted in the present study may be helpful for the treatment of patients with gastric cancer.
Our results indicated PTEN gene might induce cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway, playing a vital role in the progression of gastric cancer.