PPIB and its role in prostate cancer: associations with transcriptomic and splicing alterations.

BACKGROUND: While peptidyl-prolyl cis-trans isomerase B (PPIB) has been implicated in tumorigenesis and RNA metabolism, its specific function in prostate cancer is poorly understood. METHODS: PPIB expression was assessed in clinical prostate adenocarcinoma samples and the TCGA-PRAD cohort. In PC-3 cells, stable PPIB knockdown was achieved via lentiviral shRNA. Subsequent in vitro assays measured proliferation, apoptosis, migration, and invasion, and tumor growth was evaluated in nude mouse xenograft models. We conducted strand-specific RNA sequencing to identify differentially expressed genes (DEGs) and PPIB-associated alternative splicing events (ASEs), followed by functional enrichment analyses (GO, KEGG, and GSEA). In addition, an shRNA-resistant PPIB cDNA carrying synonymous substitutions within the sh-PPIB-275 target sequence was re-expressed in PPIB-depleted cells, followed by Transwell rescue assays. RESULTS: TCGA-PRAD analysis showed significantly higher PPIB mRNA expression in tumors. In the paired IHC cohort, an exploratory ROI-level comparison showed higher PPIB H-scores in tumor regions than in adjacent non-tumor regions (P < 0.05). Because multiple ROIs were obtained from the same patients, patient-level inference was based on ROI-averaged paired values; the mean tumor H-score was higher, but the paired difference was not statistically significant. PPIB knockdown inhibited cell proliferation, migration, invasion, and xenograft tumor growth. A modest increase in apoptotic cells was observed after PPIB depletion. Transcriptomic analysis revealed 570 differentially expressed genes and 873 altered splicing events, with enriched pathways involving DNA repair, the cell cycle, and amino acid metabolism. Integrating DEG and ASE data identified 22 overlapping genes, including the metabolic regulators PHGDH and SHMT2. Re-expression of shRNA-resistant PPIB significantly reversed the reductions in migration and invasion caused by PPIB knockdown. CONCLUSIONS: PPIB promotes prostate cancer progression and is associated with broad transcriptional and alternative splicing alterations. These results indicate a role for PPIB in prostate cancer progression and establish a foundation for investigating its post-transcriptional functions.