title: MicroRNA profiling in intraocular medulloepitheliomas.
abstract: OBJECTIVE
  To study the differential expression of microRNA (miRNA) profiles between intraocular medulloepithelioma (ME) and normal control tissue (CT).
  
  
  METHODS
  Total RNA was extracted from formalin fixed paraffin embedded (FFPE) intraocular ME (n=7) and from age matched ciliary body controls (n=8). The clinical history and phenotype was recorded. MiRNA profiles were determined using the Affymetrix GeneChip miRNA Arrays analyzed using expression console 1.3 software. Validation of significantly dysregulated miRNA was confirmed by quantitative real-time PCR. The web-based DNA Intelligent Analysis (DIANA)-miRPath v2.0 was used to perform enrichment analysis of differentially expressed (DE) miRNA gene targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.
  
  
  RESULTS
  The pathologic evaluation revealed one benign (benign non-teratoid, n=1) and six malignant tumors (malignant teratoid, n=2; malignant non-teratoid, n = 4). A total of 88 miRNAs were upregulated and 43 miRNAs were downregulated significantly (P<0.05) in the tumor specimens. Many of these significantly dysregulated miRNAs were known to play various roles in carcinogenesis and tumor behavior. RT-PCR validated three significantly upregulated miRNAs and three significantly downregulated miRNAs namely miR-217, miR-216a, miR-216b, miR-146a, miR-509-3p and miR-211. Many DE miRNAs that were significant in ME tumors showed dysregulation in retinoblastoma, glioblastoma, and precursor, normal and reactive human cartilage. Enriched pathway analysis suggested a significant association of upregulated miRNAs with 15 pathways involved in prion disease and several types of cancer. The pathways involving significantly downregulated miRNAs included the toll-like receptor (TLR) (p<4.36E-16) and Nuclear Factor kappa B (NF-κB) signaling pathways (p<9.00E-06).
  
  
  CONCLUSIONS
  We report significantly dysregulated miRNAs in intraocular ME tumors, which exhibited abnormal profiles in other cancers as well such as retinoblastoma and glioblastoma. Pathway analysis of all dysregulated miRNAs shared commonalities with other cancer pathways.
authors: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; Wilmer Eye Institute, John Hopkins University School Of Medicine, Baltimore, MD, United States of America.
authors: Deepak P
authors: DP
authors: Edward
authors: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors: Hind
authors: H
authors: Alkatan
authors: Wilmer Eye Institute, John Hopkins University School Of Medicine, Baltimore, MD, United States of America.
authors: Qundeel
authors: Q
authors: Rafiq
authors: Wilmer Eye Institute, John Hopkins University School Of Medicine, Baltimore, MD, United States of America.
authors: Charles
authors: C
authors: Eberhart
authors: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors: Saleh
authors: S
authors: Al Mesfer
authors: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors: Nicola
authors: N
authors: Ghazi
authors: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors: Leen
authors: L
authors: Al Safieh
authors: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors: Altaf A
authors: AA
authors: Kondkar
authors: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL, United States of America.
authors: Khaled K
authors: KK
authors: Abu Amero
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D051193:Toll-Like Receptors