Abstract
Purpose:
Glioblastoma (GBM) is the most common primary brain tumor with a poor therapeutic outcome. Polycomb group factor 1 (PCGF1), a member of the PcG (Polycomb group) family, is highly expressed in the developing nervous system of mice. However, the function and the mechanism of PCGF1 in GBM proliferation still remain unclear.
Methods:
Knockdown of PCGF1 was performed in U87 GBM cell by shRNA strategy via lentivirus vector. MTT assay, colony formation assays, and flow cytometry were used to measure the properties of cell proliferation and cell cycle distribution, respectively. GeneChip analysis was performed to identify the downstream effector molecules. Rescue assay was constructed to verify the screening results.
Results:
We first found that knockdown of PCGF1 led to the inhibition of U87 cells proliferation and decreased colony formation ability. The data from GeneChip expression profiling and Ingenuity Pathway Analysis (IPA) indicated that many of the altered gene cells are associated with the cell proliferation control pathways. We have further confirmed the suppression of AKT/GSK3β/c-Myc/cyclinD1 expressions by Western blotting analysis. The over-expression of c-Myc could partly restore the attenuated proliferation ability caused by knockdown of PCGF1.
Conclusion:
All the above evidences suggested that PCGF1 might be closely associated with tumorigenesis and progression of glioblastoma (GBM), in which process the oncoprotein c-Myc may participate. PCGF1 could thus be a potential therapeutic target for the treatment of glioblastoma (GBM).
Keywords:
GBM; PCGF1; cell proliferation; glioblastoma; polycomb group.