PNO1 Promotes Gastric Cancer Proliferation Through Autophagy Effect

Objective: Gastric cancer is a one of the most common malignant tumors and responsible for most mortality and morbidity of cancer worldwide.In recent years,targeted therapy and immunotherapy for gastric cancer have made great progress,but the therapeutic effect of gastric cancer is unsatisfactory due to factors such as drug resistance and recurrence.Autophagy is a programmed cell death mechanism in tumors,has attracted an increasing attention of scholars.Targeting autophagy has become an important treatment mean for tumor.PNO1 is a ribosome assembly factor,plays a pivotal role in cancer through regulating cell proliferation,invasion,autophagy,and apoptosis.However,its role in gastric cancer has not been reported.This study aims to reveal the role and regulatory mechanism of PNO1 in gastric cancer,and provide a new target for gastric cancer therapy.Methods: The information in biological database was used to analyze the expression of PNO1 in gastric cancer and paracancerous tissues,and pathologically diagnosed gastric cancer and paracancerous surgical specimens of patients in Qingdao University Affiliated Hospital were collected for immunohistochemical analysis and verification.Knockdown and overexpression of PNO1 in gastric cancer cell lines were achieved by Small interfering RNA and lentiviral vector,respectively.Western blotting and real-time quantitative PCR were used to detect the expression and transfection efficiency of PNO1 in gastric cancer cells.The effect of PNO1 on the proliferation of gastric cancer cells was detected by plate clonal formation assay and Ed U cell proliferation assay.Regulation of autophagy by PNO1 was detected using western blot and immunofluorescence.The regulatory effect of PNO1 on PI3K/AKT/mtor signaling pathway was analyzed by western blot.Finally,the mouse in situ gastric tumor bearing model was constructed to verify the role of PNO1 on gastric cancer proliferation.Results: In this study,we found that PNO1 was highly expressed in gastric cancer tissues and cells and that relatively high expression of PNO1 was associated with poor prognosis in gastric cancer patients.Overexpression of PNO1 enhanced the proliferation ability of gastric cancer cells.Knockdown of PNO1 inhibited the proliferation ability of gastric cancer in vitro and in vivo,and enhance the autophagy level of gastric cancer cells.Inhibition of autophagy reversed the decreased proliferation of gastric cancer cells caused by knockdown of PNO1.In addition,knockdown of PNO1 also inhibited the activation of PI3K/AKT/mtor signaling pathway.Conclusions: Our study shows that the high expression of PNO1 is a poor prognostic factor in gastric cancer patients,and PNO1 promotes the proliferation ability of gastric cancer by inhibiting the autophagy effect,which provides a new idea for exploring the pathogenesis of gastric cancer.Targeting the PNO1/autophagy axis has become a gastric cancer therapy.potential solutions.