PLLP inhibits the progression of wild-type p53 gastric cancer by reducing p53 protein ubiquitination by binding to TRIM59

Gastric cancer (GC) is among the most common malignant tumors worldwide. The inhibition of p53 ubiquitination can inhibit the progression of GC. The mechanism through which Plasmolipin (PLLP) regulates p53 ubiquitination in GC remains unclear. In this study, the correlation between PLLP expression and the prognosis of GC was analyzed on the basis of data from the TCGA database, and the expression characteristics of PLLP and p53 were verified by immunohistochemistry. A PLLP overexpression/knockdown GC cell model was constructed, and cell proliferation, apoptosis and invasion were detected by CCK-8, flow cytometry, and Transwell assays. Coimmunoprecipitation (Co-IP) and Western blotting were used to analyze the PLLP-TRIM59-p53 regulatory axis. The antitumor effect of PLLP in vivo was verified by tumor formation experiments in nude mice. CHX tracking assays, Co-IP and ubiquitination analysis were used to determine the effect of PLLP on p53 stability. Combined with bioinformatics prediction and experimental verification, the interaction between PLLP and the E3 ubiquitin ligase TRIM59 and its regulatory effect on the ubiquitination and degradation of p53 were analyzed. Flow cytometry and Transwell assays were used to verify the biological effect of the PLLP-TRIM59-p53 axis. We found that PLLP was downregulated in GC (P<0.05). PLLP interacts with TRIM59, inhibits TRIM59-mediated ubiquitination degradation of p53, and inhibits the progression of GC cells with wild-type p53. PLLP may be used as a potential biomarker for targeted therapy of GC.