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Integrated multi‐omic analysis of human retinoblastoma identifies novel regulatory networks
Author(s) -
Sureshbabu V.,
Mallipatna A.,
Guha N.,
SA D.,
Lateef S.,
Gundimeda S.,
Padmanabhan A.,
Shetty R.,
Ghosh A.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0544
Subject(s) - retinoblastoma , microrna , computational biology , gene expression , biology , gene , microarray , microarray analysis techniques , in vitro , dna microarray , bioinformatics , microbiology and biotechnology , genetics
Purpose a) Elucidate the differential expression profiles in tumors & invitro models. b) Identify novel signal transductions and key regulators in retinoblastoma. Methods Institutional Ethics Committee approval was obtained prior to sample collection. We used enucleated eyes of 9 case samples & 2 pediatric deceased controls. Total RNA was extracted from tumor & control retina samples for mRNA , mi RNA microarray and RT ‐ PCR for gene expression validation in tumors. Patient's aqueous, vitreous and tears were analysed by LC / GC ‐ MS to validate metabolic profiles of retinoblastoma. RB invitro models were developed using cell lines MCF ‐7, Y79 & Weri, for correlative analysis with patient data. Results We identified 8 key differentially regulated pathways and genes, from the mRNA expression profile. The mi RNA expression profile helps to discover 18 novel mi RNA s which regulates key target genes identified by mRNA microarrays. Multi‐ omics analysis of metabolomics data with gene expression profiles revealed key regulators belonging to common pathways. RB 1 silenced MCF ‐7 showed significant overlap in key cell cycle genes & RB 1 complemented retinoblastoma cell line Y79 mimics gain of function of molecular signature. Conclusions Overall, the study identifies molecular mechanisms driving retinoblastoma and provides an in‐vitro modelling framework for further studies.