Role of Epigenetics in Uveal Melanoma

Li, Yongyun; Jia, Renbing; Ge, Shengfang

doi:10.7150/ijbs.18331

Cited by 37 publications

(30 citation statements)

References 78 publications

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“…It has been reported that 1 in 8 women in her life might suffer from BC in America 2 . Recent studies have focused on identifying epigenetic signatures that are associated with tumor progression and patient prognosis to improve therapy and recovery 3 - 5 . Although some tumor suppressors and oncogenes have been identified to play central roles in tumorigenesis and development of BC 6 - 8 , the exact molecular mechanisms have not been totally elucidated.…”

Section: Introductionmentioning

confidence: 99%

MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3

Chu¹,

Liu²,

Bai³

et al. 2018

Int. J. Biol. Sci.

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Breast cancer (BC) is the most common cause of death in women throughout the world. Although microRNAs (miRNAs) have been identified as novel regulators in carcinogenesis, there are still abundant hidden treasure needed to be excavated. In the present study, we found that miR-519d expression was remarkably decreased in both human BC tissues and MCF-7 cells. CCK8 and 5-Ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound-healing and transwell assays were performed for detection of cell migration and invasion. The results demonstrated miR-519d overexpression dramatically suppressed MCF-7 cells proliferation, migration and invasion. While downregulation of miR-519d by miR-519d inhibitor substantially increased MCF-7 cell carcinogenesis. Further analysis identified Matrix Metalloproteinase-3 (MMP3) as a direct target of miR-519d. QRT-PCR and western blot results indicated the correlative expression of miR-519d and MMP3 in BC tissues and MCF-7 cells. In summary, our data uncovered the novel molecular interaction between miR-519d and MMP3, indicating a therapeutic strategy of miR-519d for BC.

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Section: Introductionmentioning

confidence: 99%

MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3

Chu¹,

Liu²,

Bai³

et al. 2018

Int. J. Biol. Sci.

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“…33,34 One of the new developments in the management of uveal melanoma is the use of microRNA molecules that play a role in gene silencing or posttranscriptional regulation of genes involved in development of uveal melanomas. 35,36 MicroRNA-34a was found to be a proapoptotic transcriptional target of the p53 tumor suppressor gene effector network. 37 MicroRNA-34a has been shown to downregulate c-Met levels, another pro-oncogenic pathway to tumor development.…”

Section: Discussionmentioning

confidence: 99%

The Interplay of MicroRNA-34a, LGR4, EMT-Associated Factors, and MMP2 in Regulating Uveal Melanoma Cells

Hou

Han

Yang

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. MicroRNA-34a (miR-34a) has been implicated in many biological processes. It is downregulated in uveal melanoma, and introduction of miR-34a inhibits the proliferation and migration of uveal melanoma cells. Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is a novel target of miR-34a identified first in retinal pigment epithelial cells. In this study, we sought to evaluate the interaction of miR-34a and LGR4 in uveal melanoma and its downstream mechanisms. METHODS. The expression of LGR4, epithelial-mesenchymal transition (EMT)-associated factors, and matrix metalloproteinase 2 (MMP2) in uveal melanoma cells was assessed by immunoblotting and immunofluorescence analysis. MicroRNA-34a mimic molecules, LGR4 small interfering RNA (siRNA), or MMP2-specific siRNA were transiently transfected into uveal melanoma cells. In vitro scratch and Transwell assays were used to evaluate the migratory and invasive potential of the resultant uveal melanoma cells. RESULTS. LGR4 is upregulated in uveal melanoma cells. Introduction of miR-34a significantly decreased the expression level of LGR4. Transfection with miR-34a or knockdown of LGR4 attenuated the aggressiveness of uveal melanoma cells. In addition, there was a decrease in the expression of mesenchymal markers N-cadherin, vimentin, and Snail following miR-34a introduction or knockdown of LGR4. Finally, MMP2 was found to be a downstream effector for miR-34a and LGR4 that regulates the migration and invasion of uveal melanoma cells. CONCLUSIONS. MicroRNA-34a negatively controls LGR4, thereby inhibiting the migration and invasion of uveal melanoma cells. Ultimately, both miR-34a and LGR4 impact the aggressiveness of uveal melanoma with alterations in the markers of the EMT. MMP2 is a downstream effector that influences the metastasis seen with uveal melanoma cells.

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“…Decitabine is a Food and Drug Administration (FDA)-approved drug for treatment of haematological malignancies, and while 3-Deazaneplanocin A is not currently FDA approved, it has been investigated for its role in inhibiting histone methylation in acute myeloid leukaemia and are therefore examples of drug repurposing opportunities for non-cancerous rare ophthalmic disease. Although retinoblastoma and uveal/intraocular melanoma are not included in this review, epigenetics and rare tumorous ophthalmic conditions have been reviewed extensively elsewhere within the last 2 years, with extensive studies illustrating the association of hypermethylation of tumour suppressor gene promoter regions and ophthalmic tumorigenesis 56 57. Therefore, the association of methylation with ophthalmic disease, coupled with attenuated retinal degeneration following methyltransferase inhibition in the two cited articles,41 53 highlights the need to conduct further investigations into epigenetic inhibitors as therapeutic agents for both tumorous and non-tumorous ophthalmic disease.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of differential methylation in rare ophthalmic diseases

et al. 2019

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Rare ophthalmic diseases have a devastating impact on a patient’s vision and consequently negatively affect their independence, ability to work and overall quality of life. Methylation is an important emerging biomarker of disease and may improve understanding of rare ophthalmic disorders. This systematic review sought to identify and evaluate literature on methylation and rare ophthalmic disease. MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and grey literature resources were searched for publications prior to 20 August 2019. Articles written in English which featured key terms such as ‘methylation’ and rare ophthalmic diseases were included. Titles, abstracts, keywords and full texts of publications were screened, as well as reference lists for reverse citations and Web of Science ‘cited reference search’ for forward citation searching. Study characteristics were extracted, and methodological rigour appraised using a standardised template. Fourteen articles were selected for full inclusion. Rare ophthalmic conditions include congenital fibrosis of extraocular muscles, retinitis pigmentosa, Fuchs endothelial corneal dystrophy, granular corneal dystrophy, choroideraemia, brittle cornea syndrome, retinopathy of prematurity, keratoconus and congenital cataracts. Outcomes include identification of methylation as contributor to disease and identification of potential novel therapeutic targets. The studies included were heterogeneous with no scope for meta-analysis following review; a narrative synthesis was undertaken. Differential methylation has been identified in a small number of rare ophthalmic diseases and few studies have been performed to date. Further multiomic research will improve understanding of rare eye diseases and hopefully lead to improved provision of diagnostic/prognostic biomarkers, and help identify novel therapeutic targets.

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Role of Epigenetics in Uveal Melanoma

Cited by 37 publications

References 78 publications

MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3

MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3

The Interplay of MicroRNA-34a, LGR4, EMT-Associated Factors, and MMP2 in Regulating Uveal Melanoma Cells

Systematic review of differential methylation in rare ophthalmic diseases

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