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E. M. Biewald; The Mir-17-92 Gene is Amplified and Overexpressed In Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2062.
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Objective:MicroRNAs are small, non-coding RNAs that regulate gene expression. They play important roles in diverse biological processes, including development, cell proliferation, differentiation and apoptosis. Aberrant microRNA expression is involved in pathogenesis and progression of human malignancies, including embryogenic tumours. Retinoblastoma is the most common eye tumour of childhood, and is mainly driven by mutations in the Rb1 gene. Genomic alterations including amplification of chromosome 6p22 have been identified in retinoblastomas, but neither high-resolution CGH nor microRNA expression have been investigated to date.
We used high-throughput real-time PCR to analyse the expression of 430 microRNAs in retinoblastomas in comparison to normal human retina. In addition, array CGH was employed to analyse gene copy number alterations in the same tumour cohort.
Among other microRNAs aberrantly expressed, the oncogenic miR-17-92 cluster was strongly overexpressed in retinoblastomas.. In addition, the gene encoding the miR-17-92 primary transcript was amplified or a gain of the respective genomic region was observed in a subset of retinoblastomas. Transfection of antagomirs (modified antisense microRNAs) into established RB cell lines led to a significant decrease in cell growth.
The oncogenic miR-17-92 cluster could be targeted as a novel treatment strategy for retinoblastomas.
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