MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2

Cheng Ying Ho, Eli Bar, Caterina Giannini, Luigi Marchionni, Matthias A. Karajannis, David Zagzag, David H. Gutmann, Charles G Eberhart, Fausto J Rodriguez

Research output: Contribution to journalArticle

Abstract

Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)-associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of-17 (miR-124),-15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA.

Original languageEnglish (US)
Pages (from-to)69-82
Number of pages14
JournalNeuro-Oncology
Volume15
Issue number1
DOIs
StatePublished - Jan 2013

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Astrocytoma
MicroRNAs
Pediatrics
Real-Time Polymerase Chain Reaction
Brain
Proteins
Neurofibromatosis 1
Oncogenes
Brain Neoplasms
Glioma
Young Adult
Immunohistochemistry
RNA

Keywords

  • BRAF
  • glioma
  • microRNA
  • neurofibromatosis
  • pilocytic astrocytoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2. / Ho, Cheng Ying; Bar, Eli; Giannini, Caterina; Marchionni, Luigi; Karajannis, Matthias A.; Zagzag, David; Gutmann, David H.; Eberhart, Charles G; Rodriguez, Fausto J.

In: Neuro-Oncology, Vol. 15, No. 1, 01.2013, p. 69-82.

Research output: Contribution to journalArticle

Ho, Cheng Ying ; Bar, Eli ; Giannini, Caterina ; Marchionni, Luigi ; Karajannis, Matthias A. ; Zagzag, David ; Gutmann, David H. ; Eberhart, Charles G ; Rodriguez, Fausto J. / MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2. In: Neuro-Oncology. 2013 ; Vol. 15, No. 1. pp. 69-82.
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abstract = "Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)-associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of-17 (miR-124),-15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA.",
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AU - Marchionni, Luigi

AU - Karajannis, Matthias A.

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AB - Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)-associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of-17 (miR-124),-15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA.

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