Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples
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Glioma constitutes one of the most common groups of brain tumors, and its prognosis is influenced by different genetic and epigenetic modulations. In this study, we demonstrated low or no expression of hedgehog interacting protein (HHIP) in most of the cell lines and primary glioma tumor samples. We further proceeded to promoter methylation study of this gene in the same cell lines and primary tumor samples and found 87 % (7/8) HHIP methylation in glioblastoma cell lines and 75 % (33/44) in primary tumor samples. These methylation pattern correlates with low or unexpressed HHIP in both cell lines and primary tumor samples. Our results suggest the possibility of epigenetic regulation of this gene in glioma, similarly to medulloblastoma, gastric, hepatic, and pancreatic cancers. Also, HHIP might be a diagnostic or prognostic marker in glioma and help to the detection of these tumors in early stages of disease.
KeywordsHuman hedgehog interacting protein (HHIP) Glioma Glioblastoma promoter methylation Melting curve analysis-Meth (MCA-Meth) GLI1
M.H. Shahi was a fellow of AECI (Agencia Española de Cooperación Internacional), Madrid, Spain. This research was supported in part by grants from the Departamento de Salud del Gobierno de Navarra, Caja Navarra (project 13912), Fundación Universitaria de Navarra, Pamplona, and Fondo de Investigación Sanitaria (PI-081849, to JSC and PI13/00055, to JAR), Madrid.
- 6.Yoon JW, Kita Y, Frank DJ, Majewski RR, Konicek BA, Nobrega MA, et al. Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J Biol Chem. 2002;277:5548–55.CrossRefPubMedGoogle Scholar
- 23.Wang TP, Hsu SH, Feng HC, Huang RF. Folate deprivation enhances invasiveness of human colon cancer cells mediated by activation of sonic hedgehog signaling through promoter hypomethylation and cross action with transcription nuclear factor-kappa B pathway. Carcinogenesis. 2012;33:1158–68.CrossRefPubMedGoogle Scholar