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Transcriptome and small RNA deep sequencing reveals deregulation of miRNA biogenesis in human glioma
Author(s) -
Moore Lynette M,
Kivinen Virpi,
Liu Yuexin,
Annala Matti,
Cogdell David,
Liu Xiuping,
Liu ChangGong,
Sawaya Raymond,
YliHarja Olli,
Shmulevich Ilya,
Fuller Gregory N,
Zhang Wei,
Nykter Matti
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4109
Subject(s) - microrna , transcriptome , biology , biogenesis , glioma , deep sequencing , gene silencing , gene , small rna , rna , gene expression , genetics , genome
Altered expression of oncogenic and tumour‐suppressing microRNAs ( miRNAs ) is widely associated with tumourigenesis. However, the regulatory mechanisms underlying these alterations are poorly understood. We sought to shed light on the deregulation of miRNA biogenesis promoting the aberrant miRNA expression profiles identified in these tumours. Using sequencing technology to perform both whole‐transcriptome and small RNA sequencing of glioma patient samples, we examined precursor and mature miRNAs to directly evaluate the miRNA maturation process, and examined expression profiles for genes involved in the major steps of miRNA biogenesis. We found that ratios of mature to precursor forms of a large number of miRNAs increased with the progression from normal brain to low‐grade and then to high‐grade gliomas. The expression levels of genes involved in each of the three major steps of miRNA biogenesis (nuclear processing, nucleo‐cytoplasmic transport, and cytoplasmic processing) were systematically altered in glioma tissues. Survival analysis of an independent data set demonstrated that the alteration of genes involved in miRNA maturation correlates with survival in glioma patients. Direct quantification of miRNA maturation with deep sequencing demonstrated that deregulation of the miRNA biogenesis pathway is a hallmark for glioma genesis and progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.