The methylation status of the platelet-derived growth factor-B gene promoter and its regulation of cellular proliferation following folate treatment in human glioma cells

• The methylation of PDGF-B gene promoter correlates with glioma grades.
• The expression of PDGF-B is affected by the methylation of PDGF-B gene promoter.
• The effect of folate on U373MG and U87MG associates with remethylation of PDGF-B.
• Folate supplementation can be a promising anti-glioma therapy.

Platelet-derived growth factor-B (PDGF-B) is a growth factor that regulates cell migration, proliferation, and differentiation, and is involved in several physical and pathological processes. The overexpression of PDGF-B in glioma surgical samples revealed its effect on tumorigenesis. In this study, we determined that the expression of PDGF-B in 54 glioma samples varied among different grades and was correlated with the cell proliferation marker, Ki-67. Using pyrosequencing, we quantitatively assessed PDGF-B gene methylation levels and determined that hypomethylation promotes increased expression of PDGF-B in higher grade gliomas. Furthermore, we treated two glioma cell lines with a demethylating agent (5-aza-2׳-deoxycitidine, 5-aza-dC) or a remethylating agent (folate) to alter the methylation status of PDGF-B. The epigenetic regulation of the PDGF-B gene not only modulated the expression levels of PDGF-B but also affected the cellular proliferation induced by TGFβ-Smad activity and the PDGF-B peptide itself. Our work showed the importance of the methylation status of the PDGF-B gene promoter, and suggests that the epigenetic regulation of the PDGF-B gene may serve as a potential therapeutic target for the inhibition of glioma proliferation.