Role of MicroRNA-182 in Posterior Uveal Melanoma: Regulation of Tumor Development through MITF, BCL2 and Cyclin D2
Open Access
- 27 July 2012
- journal article
- clinical trial
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (7), e40967
- https://doi.org/10.1371/journal.pone.0040967
Abstract
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play central roles in diverse pathological processes. In this study, we investigated the effect of microRNA-182 (miR-182) on the development of posterior uveal melanomas. Initially, we demonstrated that miR-182 expression was dependent on p53 induction in uveal melanoma cells. Interestingly, transient transfection of miR-182 into cultured uveal melanoma cells led to a significant decrease in cell growth, migration, and invasiveness. Cells transfected with miR-182 demonstrated cell cycle G1 arrest and increased apoptotic activity. Using bioinformatics, we identified three potential targets of miR-182, namely MITF, BCL2 and cyclin D2. miR-182 was shown to have activity on mRNA expression by targeting the 3′ untranslated region of MITF, BCL2 and cyclin D2. Subsequent Western blot analysis confirmed the downregulation of MITF, BCL2 and cyclin D2 protein expression. The expression of oncogene c-Met and its downstream Akt and ERK1/2 pathways was also downregulated by miR-182. Concordant with the findings that miR-182 was decreased in uveal melanoma tissue samples, overexpression of miR-182 also suppressed the in vivo growth of uveal melanoma cells. Our results demonstrated that miR-182, a p53 dependent miRNA, suppressed the expression of MITF, BCL2, cyclin D2 and functioned as a potent tumor suppressor in uveal melanoma cells.Keywords
This publication has 44 references indexed in Scilit:
- miRBase: integrating microRNA annotation and deep-sequencing dataNucleic Acids Research, 2010
- Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factorProceedings of the National Academy of Sciences of the United States of America, 2009
- Frequent somatic mutations of GNAQ in uveal melanoma and blue naeviNature, 2008
- Oncogenic BRAF Regulates Melanoma Proliferation through the Lineage Specific Factor MITFPLOS ONE, 2008
- Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes ApoptosisMolecular Cell, 2007
- A microRNA component of the p53 tumour suppressor networkNature, 2007
- Role of microphthalmia transcription factor (Mitf) in melanoma differentiationBiochemical and Biophysical Research Communications, 2007
- Mitf regulation of Dia1 controls melanoma proliferation and invasivenessGenes & Development, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Characterization of gangliosides in human uveal melanoma cellsInternational Journal of Cancer, 1991