Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications
Abstract
:1. Introduction
2. Genetic Basis of Uveal Melanoma
3. miRNA and Uveal Melanoma
miRNAs | Sample Type | Role | Regulation Action | Target | Reference |
---|---|---|---|---|---|
miR-9 | cells with highly and poorly invasive potential | tumor suppressor | suppresses cell migration and invasion | downregulation NF-κB1 | [75] |
miR-17-3p | UM patients tissues and cell lines | tumor suppressor | inhibiting cell proliferation, migration and invasion | decreased MDM2 expression | [76] |
miR-20a | cells and melanocytes, and tumor tissue samples for patients | oncogenic | increases cell growth, migration and invasion activities | not validated | [89] |
miR-21 | cell lines and tissue samples | oncogenic | promoted proliferation, migration, and invasion | inhibited expression p53 | [81] |
miR-34a | cells lines and melanocytes | tumor suppressor | inhibiting cell proliferation, migration and invasion | downregulation c-Met; decreased LGR4 | [63,64] |
miR-34b/c | cells and melanocytes from patients, the uveal stromal tissues | tumor suppressor | reduction in cell growth and migration | downregulation c-Met | [65] |
miR-122 | cell lines and patients’ tissues | tumor suppressor | impaired cell proliferation and migration | reduced expression ADAM10 and c-Met | [66] |
miR-124a | cell culture and tumor specimens | tumor suppressor | inhibited cell growth, migration and invasion | downregulation CDK4, CDK6, cyclin D2 and EZH2 | [69] |
miR-137 | cells lines from patients | tumor suppressor | decrease cell growth | downregulated MITF and CDK6 | [67] |
miR-142-3p | cells and uveal melanocytes from patients | tumor suppressor | inhibited cell proliferation, migration and invasiveness | reduced CDC25C, TGFβR1, GNAQ, WASL, and RAC1 | [77] |
miR-144 | cell lines and patients tissues | tumor suppressor | impaired cell proliferation and migration | reduced expression ADAM10 and c-Met | [66] |
miR-145 | cells with highly and low invasive potential and patients’ tissues | tumor suppressor | reduce proliferation, migration and invasion | downregulation CDC42 | [73] |
miR-155 | cell culture and tumor specimens | oncogenic | increase cell growth and invasion | inhibited NDFIP1 | [82] |
miR-181 | cell lines | oncogenic | promoted cell cycle progression | inhibited CTDSPL | [83] |
miR-182 | cells lines from patients | tumor suppressor | decrease cell growth, migration, and invasiveness | downregulation MITF, BCL2 and cyclin D2 | [68] |
miR-205 | cells with highly and low invasive potential and patients’ tissues | tumor suppressor | reduce proliferation, migration and invasion | downregulation CDC42 | [73] |
miR-216a-5p | cell lines and human embryonic kidney cell line | tumor suppressor | reduce cell proliferation | inhibit HK2 expression | [78] |
miR-222 | cell lines | oncogenic | increases proliferation and migration | decreased PI3K, Akt, MMP-9 | [87] |
miR-224-5p | cell lines and human embryonic kidney cell line and patients’ tissues | tumor suppressor | inhibited capacities of proliferation, invasion and migration | decreased PIK3R3 and AKT3 | [79] |
miR-296-3-p | choroidal tissues | tumor suppressor | inhibiting cell proliferation, cell cycle progression, migration | targeting of MMP-2 and MMP-9 in combination with FOXCUT | [90] |
miR-367 | tissue specimens, cell culture | oncogenic | promote cell proliferation and migration | reduced PTEN | [84] |
miR-454 | tumor samples from patients | oncogenic | promote cell proliferation, colony formation, invasion and induction | reduced PTEN | [85] |
miR-652 | cell lines and tissues samples from patients | oncogenic | increases proliferation and migration | decrease HOXA9 | [91] |
miRNAs as Biomarkers
4. Uveal Melanoma and DNA Methylation
5. Uveal Melanoma Biomarkers in Body Fluids
5.1. Liver Function Tests as Uveal Melanoma Biomarkers
5.2. UM-Serum Biomarkers
5.3. Ocular Fluid Proteins as Biomarkers in Uveal Melanoma
6. Current Challenges and Clinical Implications
6.1. Metastatic Risk Assessment
6.2. Tumor Tissue Analysis
6.3. Novel Treatment Options for Metastatic Uveal Melanoma
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample Type | Biomarker(s) | Type of Molecules | Significancve in Diagnosis and Prognosis | References |
---|---|---|---|---|
aqueous humor | IL-6, IL-7, IL-8, IP-10, PGF-1, MCP-1, NGF-β, EGF, b-FGF, PDGF-AA, VEGF-A, RANTES, MIP-1α, MIP-1β, TNF-α, eotaxin | cytokines, growth factors | significantly higher in UM than cataract | [122,123,124,126] |
aqueous humor | IL-8, MCP-1, angiogenin | cytokines, growth factors | differentiate between UM and benign ocular tumors | [125] |
vitreous humor | Flt-3 ligand, IL-6, IL7, IL-8, IP-10, MCP-1, MIP-1α, PDGF-AA, VEGF | cytokines, growth factors | significantly higher in UM than cataract | [126] |
aqueous humor | IP-10, MIP-1α | cytokines, growth factors | positive correlation with UM-tumor dimensions | [126] |
vitreus humor | IP-10, MIP-1α, FLT3LG, IL-6, IL-8, MCP-1 | cytokines, growth factors | positive Correlation with UM-tumor dimensions | [126] |
aqueous humor | sHLA | antigen | metastases, worse survival | [127] |
aqueous humor | VEGF-A and PLGF | growth factors | positive correlation with tumor thickness and increaly expressed after the surgery | [128] |
aqueous humor | IL-6, IL-8 and IL-1β | growth factors | increased expression after Ru-106 brachytherapy and transpupillary thermotherapy | [129] |
aqueous humor | ANG-2 | angiognesis | metastasis | [130] |
tears | Cystatin C | proteases inhibitor | diagnosis of UM | [131] |
serum | LFT | enzymes and bile pigments | metastasis, but with low predictive value | [109,110,111,112] |
serum | OPN, MIA and S-100β | tumor markers | UM hepatic metastases | [113,114,115,116] |
exosomes | interferon-γ, IL-2, IL-22 and IL-12, Pentraxin-3, TNFSF13B and TNFSF8 | interleukins and other inflammatory-related molecules | UM metastases | [117] |
serum | IGF-1 | growth factor | prediction of metastases | [118] |
serum | IL-6, CRP | interleukins and inflammatory-related molecules | early detection of irAR | [119] |
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Pašalić, D.; Nikuševa-Martić, T.; Sekovanić, A.; Kaštelan, S. Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications. Int. J. Mol. Sci. 2023, 24, 12807. https://doi.org/10.3390/ijms241612807
Pašalić D, Nikuševa-Martić T, Sekovanić A, Kaštelan S. Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications. International Journal of Molecular Sciences. 2023; 24(16):12807. https://doi.org/10.3390/ijms241612807
Chicago/Turabian StylePašalić, Daria, Tamara Nikuševa-Martić, Ankica Sekovanić, and Snježana Kaštelan. 2023. "Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications" International Journal of Molecular Sciences 24, no. 16: 12807. https://doi.org/10.3390/ijms241612807