Ras-Related Nuclear Protein-Binding Protein 9 Regulates Gastric Cancer Cell Cycle and Apoptosis Through the PTEN/PI3K/AKT Signaling Pathway

Abstract

We investigated the impact of RanBP9 on cell cycle progression and apoptosis in gastric cancer cells. RanBP9 expression was analyzed in 38 clinical gastric cancer tissues using Western blotting. Lentiviral transfection was utilized to establish GES-1 gastric cancer cell models that either overexpressed or silenced RanBP9. Cell proliferation and apoptosis were assessed using MTT and TUNEL staining assays, respectively. Apoptosis-related factors were analyzed by Western blotting and qRT-PCR. Flow cytometry and qRT-PCR were employed to evaluate cell cycle progression and the mRNA levels of CDK4/CyclinD1. The PTEN/PI3K/AKT signaling pathway was examined by Western blotting. We observed a significant reduction in RanBP9 expression in gastric cancer tissues. Overexpression of RanBP9 in GES-1 cells suppressed cell activity, enhanced apoptosis, increased Caspase3 expression and the Bax/Bcl-2 ratio, and decreased CDK4 and CyclinD1 expression, thereby preventing S phase entry. Conversely, knockdown of RanBP9 yielded opposite results. Furthermore, we found that RanBP9 negatively regulated the PTEN/PI3K/AKT pathway. Our findings demonstrate low expression of RanBP9 in gastric cancer tissues and cell lines. We have also established that RanBP9 negatively regulates the PTEN/PI3K/AKT pathway, resulting in cell cycle prolongation and promotion of apoptosis in GES-1 cells.