GLIS3 promotes the malignant biological behavior of gastric cancer cells by transcriptionally regulating PNPO to influence autophagy.

Abstract

Gastric cancer (GC) is among the most common malignant tumors worldwide and is a major contributor to increasing cancer incidence and mortality. GLIS family zinc finger 3 (GLIS3) is involved in GC progression, but its specific regulatory mechanisms remain incompletely understood. A GC tumor-bearing model was established by subcutaneously injecting MKN-45 cells into nude mice. RT‒qPCR and Western blotting were employed to detect the expression of key genes and proteins. CCK-8, colony formation, and Transwell assays were utilized to assess cell proliferation, migration, and invasion capabilities. Immunofluorescence and MDC staining were performed to examine autophagy-related indicators, and chromatin immunoprecipitation (ChIP) was performed to validate the binding of GLIS3 to the PNPO promoter. GLIS3 expression was upregulated in patients with GC and was significantly associated with shortened patient survival. GLIS3 knockdown inhibited the proliferation, migration, and invasion of MKN-45 cells in vitro and suppressed tumor growth in nude mice. Further studies revealed that GLIS3 knockdown inhibited the malignant biological behaviors of MKN-45 cells by suppressing autophagy. Additionally, GLIS3 bound to the PNPO promoter and promoted its transcription. Overexpression of PNPO increased the viability, proliferation, migration, invasion, and autophagy of MKN-45 cells in the context of GLIS3 knockdown, whereas further treatment with the autophagy inhibitor 3-MA weakened these effects. GLIS3 activates autophagy by transcriptionally regulating PNPO expression, thereby promoting the malignant biological behaviors of GC cells.