miR-193a Directly Targets PSEN1 and Inhibits Gastric Cancer Cell Growth, the Activation of PI3K/Akt Signaling Pathway, and the Epithelial-to-Mesenchymal Transition

摘要

Background . Gastric cancer, a kind of gastrointestinal malignancy, is the second type of leading death cancer. miR-193a is a key tumor suppressor in several diseases. PSEN1 is mainly related to Alzheimer’s disease and may be involved in the cleavage of the Notch receptor. Material and Methods . RT-PCR and western blot were applied to evaluate miR-193a and the expression level of PSEN1. Luciferase reporter assay was applied to verify whether PSEN1 was a target of miR-193a. The Kaplan–Meier method was employed to calculate the 5-year overall survival of gastric cancer patients. Results . miR-193a was downregulated in gastric cancer tissues and cell lines, and downregulation of miR-193a predicted poor 5-year overall survival of gastric cancer. miR-193a inhibited the proliferation and the activation of the PI3K/AKT signaling pathway in gastric cancer cells. miR-193a inhibited gastric cancer tumor growth in vivo. miR-193a impaired cell invasion and epithelial-to-mesenchymal transition (EMT) in HGC-27 cells. In addition, PSEN1 was a direct target of miR-193a and PSEN1 reversed partial functions of miR-193a in cell proliferation and invasion. Conclusion . miR-193a prominently decreased the proliferation, invasion, and activation of the PI3K/Akt signaling pathway and the abilities of epithelial-to-mesenchymal transition in gastric cancer cells. The newly identified miR-193a/PSEN1 axis provides novel insight into the pathogenesis of gastric cancer.