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Cristina Miyamoto, Claudia Martins, Shawn C. Maloney, Mohib W. Morcos, Sebastian Di Cesare, Miguel N. Burnier, Jr.; Identification Of Metastasis-Associated MicroRNAs In A Primary Uveal Melanoma And Its Metastatic Cell Line. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1423.
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Metastasis is the cause of death in approximately 40% of uveal melanoma (UM) patients within 10 years of initial diagnosis. Genes involved in regulation of the metastatic process are useful tools to elucidate molecular mechanisms and may become markers and targets for anti-metastatic therapy. In addition to biological and pathological processes, small non-coded single-stranded RNAs were recently identified as regulators of multiple genes involved in various steps of metastasis. These microRNAs can have pro or anti-metastatic effects. The purpose of this study is to identify metastasis-associated micro-RNAs in a primary UM and its correspondent metastatic melanoma cell line. Moreover, we evaluated their expression after these cell lines were treated with imatinib mesylate (IM), a compound that has been shown to abrogate the development of metastatic disease.
MicroRNA array analysis was performed using the GeneChip miRNA Array (Affymetrix Inc.) by Genome Quebec. This array contains over 40,000 probes comprising more than 7,000 probes, including controls. Levels of microRNA expression were studied in a primary UM cell line (Mel 270) and its corresponding metastatic cell line (OMM1.3). The results were analyzed using FlexArray Software. The analysis was repeated for both cell lines comparing microRNA expression before and after treatment with IM.
The results of the microRNA analysis comparing the primary and metastatic cell line revealed an increase of let7f, miR-10b, and miR-21 (4.27, 3.43 and 2.79 fold respectively) in the metastatic cell line. A second microRNA array analysis was performed on both cell lines before and after treatment with IM. In the primary uveal melanoma cell line, IM caused a significant decrease of miR21 (20%), miR29 (26%), and let7f (39%). In the metastatic uveal melanoma cell line, treatment significantly reduced let7f (59%) and miR10b (58%) expression.
Pro-metastatic microRNAs let7f, miR-10b and miR-21, which are related to angiogenesis and adhesion, migration, and invasion show increased expression in the metastatic cell line. MiR-21 and miR-29 showed decreased expression in the primary uveal melanoma cell line after treatment with imatinib mesylate whereas miR-10b was downregulated in the metastatic cell line pos-IM treatment. Moreover, let7f was reduced in both cell lines after treatment with IM. The ability of IM to downregulate the microRNA let7f in both cell lines may represent a novel pathway in which IM acts as a potent anti-angiogenic factor.
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