MicroRNA expression in medulloepitheliomas

Purpose: To study the differential expression of microRNA (miRNA) profiles between intraocular medulloepithelioma (ME) and normal control tissue. Material and methods: Total RNA was extracted from formalin fixed paraffin-embedded 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 confimed by quantitaive 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 and six malignant tumors (malignant teratoid, n=2; malignant non-teratoid, n= 4; benign non-teratoid, n=1). A total of 88 miRNAs were upregulated and 43 miRNAs were down regulated significantly in the tumor specimens (P<0.05). 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 down regulated miRNAs namely miR-217,miR-216a,miR-216b,miR-146a.miR-509-3p and miR-211. 56 miRNAs were significantly dysregulated in teratoid versus non-teratoid malignant tumors. Many DE miRNAs that were significant in ME tumors showed dysregulation in retinoblastoma, and glioblastoma. Several miRNAs in teratoid tumors were significantly up-regulated as in 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 down-regulated miRNAs included the toll-like receptor (p<4.36E-16) and NF-kappa B 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. Compared expression profiles of 7 tumor and 8 control samples. The 7 tumor smaples were charcaterized as bening_teratoid (n=1), malignant_teratoid (n = 2) and malignant_non-teratoid (n=4). Malignant_teratoid and malignant_non-teratoid were compared against each other for further analysis.