PRPF4 Knockdown Suppresses Glioblastoma Progression the p38 MAPK and ERK Signaling Pathways.

Background/aim: Pre-mRNA processing factor 4 (PRPF4), a core protein of U4/U6 small nuclear ribonucleoproteins (snRNPs), is crucial for maintaining their structure by interacting with PRPF3 and Cyclophilin H. Beyond its role in splicing, PRPF4 has been implicated in cell survival, apoptosis, and oncogenesis. Although PRPF4 mutations have been associated with retinitis pigmentosa, its role in glioblastoma (GBM) remains unclear. This study aimed to investigate the function of PRPF4 in GBM progression and its potential as a therapeutic target.

Materials And Methods: Gene expression profiling was conducted to compare PRPF4 levels between GBM tumors and normal tissues. PRPF4 expression was also evaluated in various cancer and GBM cell lines. Stable PRPF4 knockdown cell lines were established using A172 and T98G GBM cell lines. Cellular proliferation, apoptosis, migration, and invasion were assessed through gene expression and functional assays. Additionally, molecular pathways affected by PRPF4 knockdown were examined, focusing on the p38 MAPK signaling pathway. Finally, metabolic processes in PRPF4 knockdown cells were estimated through proteomic analysis.

Results: PRPF4 expression was elevated in GBM. Knockdown of PRPF4 reduced cell proliferation, induced apoptosis, and suppressed migration and invasion in GBM cells. PRPF4 knockdown also suppressed MKK3/6-p38-ATF2 and RAS-MEK-ERK1/2 signaling pathways. Proteome analysis revealed disruptions in metabolic pathways, including glutathione and carbon metabolisms, which are associated with GBM progression.

Conclusion: PRPF4 knockdown inhibits GBM progression by reducing p38 MAPK and ERK signaling cascade with metabolic alterations. Targeting PRPF4 may offer novel therapeutic strategies for GBM treatment.