PCBP2 stabilizes TROAP to promote the malignant progression of gastric cancer.

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Poly(rC) binding protein 2 (PCBP2), an RNA binding protein, has been reported to be involved in the progression of various cancers. However, the role of PCBP2 in GC and its underlying mechanisms remain elusive. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect mRNA expression, whereas western blotting and immunohistochemistry assays were used to detect protein expression levels. Cell proliferation, migration, and invasion were assessed by EdU assay, wound-healing assay, and transwell assay, respectively. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and iron (Fe) were detected using commercial assay kits. RIP assay was conducted to analyze the relationship between PCBP2 and trophinin-associated protein (TROAP). Actinomycin D assay was performed to investigate the effect of PCBP2 depletion on TROAP mRNA stabilization. Finally, a subcutaneous xenograft mouse model was established to validate the effect of PCBP2 depletion on tumor formation. PCBP2 expression was upregulated in GC tissues and cells, and its depletion inhibited GC cell proliferation, migration, and invasion. Additionally, PCBP2 depletion promoted ferroptosis, a novel form of cell death mediated by iron. TROAP expression was also upregulated in GC tissues and cells, and PCBP2 stabilized TROAP mRNA expression in GC cells. Knocking down PCBP2 regulated GC cell proliferation, migration, invasion, and ferroptosis by reducing TROAP expression. Furthermore, PCBP2 knockdown repressed aggressive behavior of GC cells in vivo. Our study demonstrated that PCBP2 stabilized TROAP to promote the malignant progression of gastric cancer. Targeting PCBP2 and its downstream target TROAP may provide a novel therapeutic strategy for the treatment of gastric cancer.