title: Genome-wide small noncoding RNA profiling of pediatric high-grade gliomas reveals deregulation of several miRNAs, identifies downregulation of snoRNA cluster HBII-52 and delineates H3F3A and TP53 mutant-specific miRNAs and snoRNAs.
abstract: Pediatric high-grade gliomas (HGGs) are highly malignant tumors that remain incurable and relatively understudied. The crucial role of noncoding RNAs (ncRNAs) has been reported in various cancers. However, the study on miRNAs in pediatric HGGs is scant and there is no report till date on the status of other small ncRNAs. Genome-wide microarray analysis was performed to investigate small ncRNA expression in pediatric HGG (n = 14) and compared to adult glioblastoma (GBM) signature. The validation of miRNAs and small nucleolar RNAs (snoRNAs) was done by real-time polymerase chain reaction. TP53 and H3F3A mutation-specific miRNA and snoRNA profiles were generated and analyzed. Pediatric HGGs showed upregulation of miR-17/92 and its paralog clusters (miR106b/25 and miR-106a/363), whereas majority of downregulated miRNAs belonged to miR379/656 cluster (14q32). Unsupervised hierarchical clustering identified two distinct groups. Interestingly, Group 2 with downregulated 14q32 cluster showed better overall survival. The miRNAs unique to pediatric HGG as compared to adult GBM were predicted to affect PDGFR and SMAD2/3 pathways. Similarities were seen between pediatric HGG and TP53 mutant miRNA profiles as compared to wild types. Several of H3F3A mutation-regulated genes were found to be the targets of H3F3A mutant-specific miRNAs. Remarkably, a significant downregulation of HBII-52 snoRNA cluster was found in pediatric HGGs, and was specific to H3F3A nonmutants. This is the first genome-wide profiling study on miRNAs and snoRNAs in pediatric HGGs with respect to H3F3A and TP53 mutations. The comparison of miRNA profiles of pediatric HGGs and adult GBM reiterates the overlaps and differences as also seen with their gene expression and methylation signatures.
authors.affiliation: Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi, India.
authors.forename: Prerana
authors.initials: P
authors.lastname: Jha
authors.affiliation: Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pathak
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Suvendu
authors.initials: S
authors.lastname: Purkait
authors.affiliation: Department of Radiotherapy, Dr B R Ambedkar Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Supriyo
authors.initials: S
authors.lastname: Mallik
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Mehar
authors.initials: M
authors.lastname: Chand Sharma
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Suri
authors.affiliation: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Sharma
authors.affiliation: Department of Radiotherapy, Dr B R Ambedkar Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: P K
authors.initials: PK
authors.lastname: Julka
authors.affiliation: Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Kulshreshtha
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006657:Histones / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020537:RNA, Small Nucleolar / Q000235:genetics*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D006657:Histones; D035683:MicroRNAs; D020537:RNA, Small Nucleolar; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: H3F3A; TP53; miRNA; pediatric GBM; small nucleolar RNA