NDLI: MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma.

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MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma.

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MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chen, Xiaoyan Tang, Jiang Yan, Dongsheng Dong, Xiang Da Wang, Jiao He, Dandan Tu, LiLi Dong, Feng Wang, Lihua Hu, Dan-Ning
Description	Country affiliation: China Author Affiliation: Chen X ( School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.)
Abstract	PURPOSE: MicroRNA-124a (miR-124a), an abundant microRNA in the central neuron system, has been linked to tumor progression. Here, we investigated the role of miR-124a in uveal melanoma development. METHODS: Expression of miR-124a in uveal melanoma cells was examined using real time RT-PCR. The effect of miR-124a on cell proliferation, migration, and invasion was analyzed using MTS assay, flow cytometry, and transwell experiments. The ability of miR-124a to repress tumor growth was tested in vivo. Target genes of miR-124a were first predicted by bioinformatics, confirmed using a luciferase assay, and their expression determined by Western blotting. DNA methylation and histone modification of miR-124a was analyzed by methylation-specific PCR and ChIP assay. Finally, epigenetic drugs were used to alter the expression of miR-124a. RESULTS: miR-124a expression was downregulated in both uveal melanoma cells and clinical specimens. Transient transfection of miR-124a into uveal melanoma cells inhibited cell growth, migration, and invasion. Moreover, introduction of miR-124a suppressed in vivo growth of tumor. Potential targets of miR-124a were found to include CDK4, CDK6, cyclin D2, and EZH2. Knockdown of EZH2 by siRNA resulted in inhibition of uveal melanoma cell migration and invasion. In addition, miR-124a expression was found to be regulated via epigenetic mechanisms, with its expression restored when cells were treated with a DNA hypomethylating agent, 5-aza-2'-deoxycytidine, and a histone deacetylase inhibitor, trichostatin A. CONCLUSIONS: Our results demonstrated that miR-124a could function as a potent tumor suppressor by regulation of multiple targets, and was epigenetically silenced in the development of uveal melanoma.
ISSN	01460404
e-ISSN	15525783
Journal	Investigative Opthalmology & Visual Science
Issue Number	3
Volume Number	54
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Epigenesis, Genetic Physiology Eye Neoplasms Metabolism Melanoma Micrornas Tumor Suppressor Proteins Uveal Neoplasms Blotting, Western Cell Movement Cell Proliferation Dna Methylation Down-regulation Genetics Pathology Flow Cytometry Gene Expression Regulation, Neoplastic Neoplasm Invasiveness Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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