gms | German Medical Science

MicroRNAs are small non-coding RNAs regulating 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 embryonic tumours. Retinoblastoma is the most common eye tumour of childhood and is mainly driven by mutations in the Rb1-gene. Genomic alterations observed in retinoblastoma include amplification of chromosome 6p22 but neither high-resolution CGH nor microRNA expression have been investigated so far. To address these issues, we used high throughput real-time PCR to analyse the expression of 430 microRNAs in retinoblastomas in comparison to normal human retina. In addition, we used aCGH to analyse gene copy number alterations in the same tumour cohort. Among other microRNAs aberrantly expressed, the oncogenic miR-17-92 cluster was highly expressed in retinoblastoma in contrast to normal retinal cells. 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. Furthermore, we could show that adding of antagomirs (modified antisense micro-RNAs) to established RB cell lines resulted in a growth reduction in MTT-essays.Therefore microRNAs could be a target for the treatment of retinoblastoma in future as antagomirs could be employed to block oncogenic microRNAs.