title: Identification and Insilico Analysis of Retinoblastoma Serum microRNA Profile and Gene Targets Towards Prediction of Novel Serum Biomarkers.
abstract: Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient's serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change ≤ -2.0, P ≤ 0.05) and 24 to be downregulated (fold change ≥ +2.0, P ≤ 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway.
authors: L & T Ocular Pathology Department, Kamalnayan Bajaj Research Institute, Vision Research Foundation, Sankara Nethralaya, Tamil Nadu, India. ; Shanmugha Arts, Science, Technology & Research Academy (SASTRA University), Tirumalaisamudram, Thanjavur, Tamil Nadu, India.
authors: Madhu
authors: M
authors: Beta
authors: Nalini
authors: N
authors: Venkatesan
authors: Madavan
authors: M
authors: Vasudevan
authors: Umashankar
authors: U
authors: Vetrivel
authors: Vikas
authors: V
authors: Khetan
authors: Subramanian
authors: S
authors: Krishnakumar
keywords: bioinformatics tools; biomarkers; micro RNA; retinoblastoma
references: Crit Rev Oncol Hematol. 2011 Nov;80(2):193-208
references: 21145252
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3903-8
references: 18308936
references: J Cell Mol Med. 2011 Jul;15(7):1593-602
references: 20716115
references: Pediatr Hematol Oncol. 1998 Nov-Dec;15(6):501-8
references: 9842643
references: Ophthalmology. 2012 Jul;119(7):1470-7
references: 22463820
references: Cancer Res. 2005 Nov 1;65(21):9628-32
references: 16266980
references: PLoS One. 2012;7(6):e39309
references: 22745731
references: J Pediatr Ophthalmol Strabismus. 2005 Mar-Apr;42(2):75-81; quiz 112-3
references: 15825743
references: J Integr Bioinform. 2010 Mar 25;7(3):
references: 20375447
references: Nat Methods. 2007 Dec;4(12):1045-9
references: 18026111
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Cancer Epidemiol. 2012 Feb;36(1):e61-7
references: 22018950
references: Mol Vis. 2010 Jul 13;16:1292-303
references: 20664703
references: Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4542-51
references: 19443717
references: Pediatr Blood Cancer. 2006 Nov;47(6):801-5
references: 16358310
references: Genomics. 2007 Sep;90(3):344-53
references: 17604597
references: Clin Cancer Res. 2009 Sep 1;15(17):5473-7
references: 19706812
references: Genes Dev. 2011 Aug 15;25(16):1734-45
references: 21816922
references: J Biomed Biotechnol. 2011;2011:597145
references: 21716661
references: BMC Mol Biol. 2008 Aug 21;9:76
references: 18718003
references: Gene. 2006 Jan 3;365:2-10
references: 16356665
references: Pediatr Blood Cancer. 2008 Feb;50(2):402-6
references: 17091485
references: J Pediatr Hematol Oncol. 2011 Oct;33(7):529-33
references: 21941147
references: Nature. 2012 Jan 11;481(7381):329-34
references: 22237022
references: Bioinformatics. 2008 Feb 1;24(3):325-32
references: 18048393
references: J Clin Oncol. 2010 Oct 10;28(29):e573-4; author reply e575-6
references: 20697097
references: Lancet. 2012 Apr 14;379(9824):1436-46
references: 22414599
references: PLoS One. 2011 Feb 24;6(2):e16408
references: 21383985
references: Biochimie. 2012 Sep;94(9):1910-7
references: 22627383
references: Ophthalmol Clin North Am. 2005 Mar;18(1):41-53, viii
references: 15763190
references: Mol Cancer. 2007 Aug 07;6:50
references: 17683638
references: Eur J Cancer. 2011 Mar;47(5):784-91
references: 21112772
references: Cancer Sci. 2009 Jul;100(7):1234-42
references: 19486339
references: PLoS Comput Biol. 2009 Sep;5(9):e1000513
references: 19779543
references: Br J Cancer. 2010 Mar 30;102(7):1174-9
references: 20234369
references: Cancer Sci. 2011 Mar;102(3):522-9
references: 21166959
references: Mol Vis. 2012;18:2279-87
references: 22969266
references: Genes Dev. 2007 May 1;21(9):1025-30
references: 17437991
references: Cancer Lett. 2011 Oct 1;309(1):62-70
references: 21664042
references: Dig Dis Sci. 2012 Apr;57(4):897-904
references: 22198701
references: Int J Oncol. 2011 Nov;39(5):1183-92
references: 21769427
references: Childs Nerv Syst. 2009 Jan;25(1):13-20
references: 18818933
references: Genome Res. 2009 Mar;19(3):481-90
references: 19088304
references: PLoS One. 2012;7(4):e35561
references: 22558167
references: PLoS One. 2012;7(2):e32230
references: 22393390
references: Arch Pathol Lab Med. 2011 Aug;135(8):1017-23
references: 21809993
references: PLoS One. 2012;7(9):e44398
references: 22970209
references: BMC Bioinformatics. 2011 Dec 21;12:488
references: 22188670