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26682910
Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.

Acta Neuropathol Commun, 2015/12/18;3:86.

Jones TA[1], Jeyapalan JN[1], Forshew T[1, 2], Tatevossian RG[1, 3], Lawson AR[1, 4], Patel SN[1], Doctor GT[1], Mumin MA[1], Picker SR[5, 6], Phipps KP[7], Michalski A[8], Jacques TS[9, 10], Sheer D[11]

Affiliations

PMID: 26682910DOI: 10.1186/s40478-015-0266-3

Impact factor: 7.578

Abstract
introduction: Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas.
results: Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B.
conclusion: These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs.
MeSH terms
Adolescent; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Female; Gene Expression Profiling; Humans; Infant; Male; MicroRNAs; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Signal Transduction
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