title: Transcriptome and small RNA deep sequencing reveals deregulation of miRNA biogenesis in human glioma.
abstract: 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.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Moore
authors.forename: Virpi
authors.initials: V
authors.lastname: Kivinen
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Liu
authors.forename: Matti
authors.initials: M
authors.lastname: Annala
authors.forename: David
authors.initials: D
authors.lastname: Cogdell
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D017423:Sequence Analysis, RNA / Q000379:methods*; D015996:Survival Rate; D013781:Texas / Q000453:epidemiology; D059467:Transcriptome
chemical_list: D035683:MicroRNAs