Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial-mesenchymal transition.

BACKGROUND

Gliomas are aggressive brain tumors with high mortality and recurrence rates. Pleiotrophin (PTN), a cytokine that interacts with heparin, is upregulated in several cancers, including breast and lung cancer. PTN is implicated in cancer progression, recurrence, epithelial-mesenchymal transition (EMT), and metastasis. However, the role of PTN in glioma progression remains poorly understood. This study aimed to investigate the expression profile of PTN in glioma and its potential prognostic significance.

METHODS

The expression levels of PTN in glioma samples were analyzed using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify PTN-associated pathways. In vitro experiments were performed to assess the impact of PTN suppression on glioma cell growth, cell cycle progression, migration, and invasion. In addition, gene set enrichment analysis (GSEA) and Western blot were employed to investigate the link between PTN and NF-κB signaling pathways.

RESULTS

PTN expression was significantly higher in glioma samples, and elevated PTN levels were associated with decreased overall survival. GO term and KEGG analysis showed that PTN is primarily linked to pathways related to cell mitosis, including the cell cycle and DNA replication. In vitro experiments demonstrated that the suppression of PTN inhibited glioma cell growth, arrested the cell cycle in the G0/G1 phase, and impaired the migratory and invasive capabilities of glioma cells. GSEA revealed a significant correlation between PTN and the NF-κB pathway. Further investigation showed that PTN suppression inhibited NF-κB activation and IκB phosphorylation, thereby preventing Slug-induced EMT in glioma cells.

CONCLUSIONS

PTN plays a crucial role in glioma progression by regulating cell proliferation, migration, invasion, and EMT through the NF-κB pathway. PTN may serve as an important prognostic biomarker and therapeutic target in glioma treatment.