P4HA3 Promotes Clear Cell Renal Cell Carcinoma Progression via the PI3K/AKT/GSK3β Pathway

Abstract

Abstract Purpose Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. P4HA3 is a key enzyme in collagen biosynthesis and has emerged as important molecules in regulation of proliferation, invasion, and metastasis in various tumor types. The role of P4HA3 in the development of ccRCC has remained to be elucidated. Methods Genes expression, prognostic, and enrichment analyses were carried out with bioinformatics analysis. The efficiency of P4HA3 knockdown was confirmed by real-time quantitative PCR and western blotting. The cellular functions were analyzed by CCK-8, EdU, wound healing, and transwell assays. The levels of related proteins expression were analyzed by western blotting. Results P4HA3 was highly expressed in ccRCC compared with normal tissue samples from the TCGA database. Kaplan-Meier curves results showed that the expression level of P4HA3 was significantly negatively correlated with overall survival of patients. P4HA3 expression knockdown inhibited the proliferation, migration, and invasion of ccRCC cells, as demonstrated by in vitro experiments. In addition, GSEA results revealed that P4HA3 may be related to EMT and involved in the PI3K-AKT-GSK3β pathway in ccRCC; this was tentatively confirmed through western blotting. Conclusion P4HA3 may induce ccRCC progression via the PI3K-AKT-GSK3β signaling pathway and could represent a potential therapeutic target.