PCGF1 Promotes the Tumorigenesis of Malignancies Through Upregulating CCDC34 in Glioma.

BACKGROUND

Polycomb group factor 1 (PCGF1) and coiled-coil domain-containing protein 34 (CCDC34) have been implicated in tumorigenesis in multiple malignancies. However, their biological functions and prognostic significance in glioma remain poorly defined.

METHODS

RNA-sequencing data from glioma cell lines with PCGF1 knockdown were obtained from the GEO database. Correlations between PCGF1 and CCDC34 expression were analyzed using datasets from TCGA, CGGA, and GEO. In addition, RT-qPCR was performed to quantify PCGF1 and CCDC34 expression in glioma specimens. Kaplan-Meier survival analyses were conducted to evaluate the prognostic value of CCDC34. Functional assays were performed using cell lines with PCGF1 or CCDC34 knockdown and overexpression to assess their roles in glioma progression and to elucidate their regulatory relationship. Cell proliferation and colony formation assays were carried out to evaluate tumorigenic capacity.

RESULTS

CCDC34 expression was significantly downregulated in glioma cell lines following PCGF1 knockdown compared with controls. CCDC34 expression positively correlated with WHO tumor grade in glioma. Elevated CCDC34 expression was significantly associated with poorer patient outcomes. Functionally, CCDC34 expression was closely linked to enhanced cell proliferation and colony-forming ability. Rescue experiments demonstrated that PCGF1 promotes glioma cell proliferation in a CCDC34-dependent manner. Gene set enrichment analysis (GSEA) further revealed that both PCGF1 and CCDC34 expression were positively associated with hypoxia, coagulation, and epithelial-mesenchymal transition (EMT) signaling pathways.

CONCLUSION

Our findings demonstrate that PCGF1 promotes glioma proliferation in a CCDC34-dependent manner and suggest that CCDC34 may serve as a novel prognostic biomarker and potential therapeutic target in glioma.