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Tumor Biology
Published in: Tumor Biology 4/2015

01-04-2015 | Research Article

Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples

Authors: Mehdi H. Shahi, Idoya Zazpe, Mohammad Afzal, Subrata Sinha, Robert B. Rebhun, Bárbara Meléndez, Juan A. Rey, Javier S. Castresana

Published in: Tumor Biology | Issue 4/2015

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Abstract

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.
Literature
1.
Dahmane N, Ruiz i Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development. 1999;126:3089–100.PubMed
2.
Fu M, Lui VC, Sham MH, Pachnis V, Tam PK. Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut. J Cell Biol. 2004;166:673–84.CrossRefPubMedPubMedCentral
3.
Fuccillo M, Joyner AL, Fishell G. Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci. 2006;7:772–83.CrossRefPubMed
4.
Preat T, Therond P, Lamour-Isnard C, Limbourg-Bouchon B, Tricoire H, Erk I, et al. A putative serine/threonine protein kinase encoded by the segment-polarity fused gene of Drosophila. Nature. 1990;347:87–9.CrossRefPubMed
5.
Sisson JC, Ho KS, Suyama K, Scott MP. Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway. Cell. 1997;90:235–45.CrossRefPubMed
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.CrossRefPubMed
7.
Chuang PT, Kawcak T, McMahon AP. Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung. Genes Dev. 2003;17:342–7.CrossRefPubMedPubMedCentral
8.
Chuang PT, McMahon AP. Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein. Nature. 1999;397:617–21.CrossRefPubMed
9.
Martin ST, Sato N, Dhara S, Chang R, Hustinx SR, Abe T, et al. Aberrant methylation of the Human Hedgehog interacting protein (HHIP) gene in pancreatic neoplasms. Cancer Biol Ther. 2005;4:728–33.CrossRefPubMed
10.
Tada M, Kanai F, Tanaka Y, Tateishi K, Ohta M, Asaoka Y, et al. Down-regulation of hedgehog-interacting protein through genetic and epigenetic alterations in human hepatocellular carcinoma. Clin Cancer Res. 2008;14:3768–76.CrossRefPubMed
11.
Taniguchi H, Yamamoto H, Akutsu N, Nosho K, Adachi Y, Imai K, et al. Transcriptional silencing of hedgehog-interacting protein by CpG hypermethylation and chromatic structure in human gastrointestinal cancer. J Pathol. 2007;213:131–9.CrossRefPubMed
12.
Shahi MH, Afzal M, Sinha S, Eberhart CG, Rey JA, Fan X, et al. Human hedgehog interacting protein expression and promoter methylation in medulloblastoma cell lines and primary tumor samples. J Neurooncol. 2011;103:287–96.CrossRefPubMed
13.
Chun SG, Zhou W, Yee NS. Combined targeting of histone deacetylases and hedgehog signaling enhances cytoxicity in pancreatic cancer. Cancer Biol Ther. 2009;8:1328–39.CrossRefPubMed
14.
Shahi MH, Lorente A, Castresana JS. Hedgehog signalling in medulloblastoma, glioblastoma and neuroblastoma. Oncol Rep. 2008;19:681–8.PubMed
15.
Katoh Y, Katoh M. Comparative genomics on HHIP family orthologs. Int J Mol Med. 2006;17:391–5.PubMed
16.
Li LC, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002;18:1427–31.CrossRefPubMed
17.
Lorente A, Mueller W, Urdangarin E, Lazcoz P, von Deimling A, Castresana JS. Detection of methylation in promoter sequences by melting curve analysis-based semiquantitative real time PCR. BMC Cancer. 2008;8:61.CrossRefPubMedPubMedCentral
18.
Utikal J, Gratchev A, Muller-Molinet I, Oerther S, Kzhyshkowska J, Arens N, et al. The expression of metastasis suppressor MIM/MTSS1 is regulated by DNA methylation. Int J Cancer. 2006;119:2287–93.CrossRefPubMed
19.
Wang LH, Choi YL, Hua XY, Shin YK, Song YJ, Youn SJ, et al. Increased expression of sonic hedgehog and altered methylation of its promoter region in gastric cancer and its related lesions. Mod Pathol. 2006;19:675–83.CrossRefPubMed
20.
Fu X, Yang X, Li J, Tian X, Cai J, Zhang Y. Opposite expression patterns of Sonic hedgehog and Indian hedgehog are associated with aberrant methylation status of their promoters in colorectal cancers. Pathology. 2010;42:553–9.CrossRefPubMed
21.
Shahi MH, Schiapparelli P, Afzal M, Sinha S, Rey JA, Castresana JS. Expression and epigenetic modulation of sonic hedgehog-GLI1 pathway genes in neuroblastoma cell lines and tumors. Tumour Biol. 2011;32:113–27.CrossRefPubMed
22.
Shahi MH, Afzal M, Sinha S, Eberhart CG, Rey JA, Fan X, et al. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma. BMC Cancer. 2010;10:614.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
24.
Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85:841–51.CrossRefPubMed
25.
Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 1996;272:1668–71.CrossRefPubMed
26.
Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998;391:90–2.CrossRefPubMed
27.
Zurawel RH, Allen C, Chiappa S, Cato W, Biegel J, Cogen P, et al. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer. 2000;27:44–51.CrossRefPubMed
28.
Eichenmuller M, Gruner I, Hagl B, Haberle B, Muller-Hocker J, von Schweinitz D, et al. Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatology. 2009;49:482–90.CrossRefPubMed
29.
Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846–51.CrossRefPubMed
Metadata
Title
Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples
Authors
Mehdi H. Shahi
Idoya Zazpe
Mohammad Afzal
Subrata Sinha
Robert B. Rebhun
Bárbara Meléndez
Juan A. Rey
Javier S. Castresana
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2846-4

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