1. Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.
- Author
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Jones TA, Jeyapalan JN, Forshew T, Tatevossian RG, Lawson AR, Patel SN, Doctor GT, Mumin MA, Picker SR, Phipps KP, Michalski A, Jacques TS, and Sheer D
- Subjects
- Adolescent, Child, Child, Preschool, Female, Gene Expression Profiling, Humans, Infant, Male, Mitogen-Activated Protein Kinase Kinases metabolism, NF-kappa B genetics, NF-kappa B metabolism, Oligonucleotide Array Sequence Analysis, RNA, Messenger metabolism, Signal Transduction genetics, Astrocytoma genetics, Astrocytoma metabolism, Brain Neoplasms genetics, Brain Neoplasms metabolism, MicroRNAs metabolism, Signal Transduction drug effects
- 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.
- Published
- 2015
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