Purchase this article with an account.
Xiaoyan Chen, Jiao Wang, Huanjun Shen, Juan Lu, Canxia Li, Dan-Ning Hu, Xiang Da Dong, Dongsheng Yan, LiLi Tu; Epigenetics, MicroRNAs, and Carcinogenesis: Functional Role of MicroRNA-137 in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2011;52(3):1193-1199. doi: 10.1167/iovs.10-5272.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
MicroRNAs (miRNAs) can contribute to tumorigenesis by acting as either oncogenes or tumor suppressor genes. The authors' previous studies on miR-34a showed that miRNA can influence the growth of uveal melanoma cells. In this study, they investigated the role of miR-137 in the pathogenesis of uveal melanoma.
Real-time RT-PCR was used to screen the expression levels of miR-137 in uveal melanocytes and uveal melanoma cell lines. Cell proliferation was examined by MTS assay and cell cycle was analyzed by flow cytometry. The target genes of miR-137 were predicted by bioinformatics and confirmed using a luciferase reporter assay. The expression of MITF, CDK6, and cell cycle regulatory proteins was determined by Western blot analysis. The ability to increase miR-137 expression by epigenetic drugs was tested using real-time RT-PCR.
miR-137 expression was lower in uveal melanoma cell lines than in uveal melanocytes. Ectopic transfection of miR-137 into uveal melanoma cells induced G1 cell cycle arrest, leading to a significant decrease in cell growth. Overexpression of miR-137 downregulated MITF, a transcription factor with oncogenic activity. Moreover, the introduction of miR-137 downregulated the oncogenic tyrosine kinase protein receptor c-Met and cell cycle–related proteins, including CDK6. One avenue to increase the expression levels of miR-137 was through treatment with a DNA hypomethylating agent, 5-aza-2′-deoxycytidine, and a histone deacetylase inhibitor, trichostatin A.
The results showed that miR-137 can act as a tumor suppressor in uveal melanoma cell proliferation through downregulation of the targets MITF and CDK6. miR-137 may be epigenetically silenced during uveal melanoma tumorigenesis.
This PDF is available to Subscribers Only