Suppression of NSUN2 Enhances the Sensitivity to Chemosensitivity and Inhibits Proliferation by Mediating Cell Apoptosis in Gastric Cancer

NSUN2 is a critical methyltransferase for adding m5C to RNA. Its upregulation promotes the growth and metastasis of several tumors including gastric cancer (GC). However, it is unclear if NSUN2 can improve the chemosensitivity of GC to treatment with therapeutic agents such as cisplatin (CDDP) and 5-fluorouracil (5-FU). Flow cytometry was used to measure the effects of knocked-down NSUN2 expression on GC cell apoptosis and cell cycle progression. Western blot analysis examined specific signaling pathways through which NSUN2 mediates control of responses underlying the GC tumorous phenotype. NSUN2 expression was upregulated in GC tissues and its levels of rises were related to the extent of lymph node metastasis and increases in Ki67 proliferative marker expression. NSUN2 shRNA transfection suppressed rises in ERK1/2 phosphorylation status and downregulated anti-apoptosis protein Bcl-2 and upregulated pro-apoptosis protein Bax. Overall, the results reveal that NSUN2 downregulation promotes the GC chemosensitivity to inverse modulation by chemotherapeutic agents of Bcl-2 and Bax expression levels and declines in ERK1/2-induced proliferation. Our results indicate that inhibition of NSUN2 activation may be an effective procedure to enhance the efficacy of chemotherapeutic agents used to clinically treat GC.