Isocitrate dehydrogenase (IDH) mutations occur frequently in lower-grade
gliomas, which result in genome-wide epigenetic alterations. The wild-type IDH1 is reported to participate in
lipid biosynthesis and
amino acid metabolism, but its role in
tumorigenesis is still unclear. In this study, the expressions of IDH1 and podoplanin (Pdpn) were determined in IDH-mutated and IDH-wild-type
gliomas, and their relationships in
glioma were further analyzed. In addition, the regulation of wild-type IDH1 and mutant IDH1 on Pdpn expression was investigated by
luciferase assays and promoter methylation analysis. Our study showed that Pdpn was almost undetectable in IDH-mutated
glioma but strongly expressed in higher-grade IDH-wild-type
glioma. Pdpn overexpression promoted the migration of
glioma cells but had little effect on cell growth. Moreover, Pdpn expression was positively correlated with the increased wild-type IDH1 levels in IDH-wild-type
glioma. Consistently, the wild-type IDH1 greatly promoted the transcription and expression of Pdpn, but the mutant IDH1 and
D-2-hydroxyglutarate significantly suppressed Pdpn expression in
glioma cells. Besides, our results revealed that the methylation of CpG islands in the Pdpn promoter was opposingly regulated by wild-type and mutant IDH1 in
glioma. Collectively, our results indicated that wild-type and mutant IDH1 opposingly controlled the Pdpn expression in
glioma by regulating its promoter methylation, which provides a basis for understanding the relationship between wild-type and mutant IDH1 in epigenetic regulation and
tumorigenesis.