Table 2.
Regulatory effects in cutaneous or uveal melanoma of upregulated microRNA found in plasma and extracellular vesicles in vitreous humor, peripheral blood, blood collected during isolated liver perfusion, and/or UM-tissue. Expression compared to: UM-patients versus healthy controls; Metastatic patients versus localized disease; Monosomy 3 versus disomy 3. Abbreviations: DE: differentially expressed; RT-PCR: reverse transcription polymerase chain reaction; EVs: extracellular vesicles; TLDA: Taqman low density array; RT2 array: Qiagen RT2 miRNA PCR array (brain cancer panel); qNPA: HTG molecular diagnostics quantitative nuclease protection assay; VH: vitreous humor.
| microRNA | Expression | Found in Tissue Type | Sequencing Technique | Modulatory Effect |
|---|---|---|---|---|
| miR-20a [97] | Upregulated in UM-patients and metastatic patients |
Plasma | RT-PCR | Promotes cell proliferation and migration by modulation of the cell cycle, focal adhesion and phosphoinositide 3-kinase (PI3K)-AKT signaling pathway [103,104]. |
| miR-20a [98] | Not DE between monosomy and disomy 3 | Plasma | RT-PCR | |
| miR-21 [94] | Upregulated in UM-patients |
EVs: vitreous and FFPE UM-Tissue | TLDA | Promotes tumor growth, invasion, and metastasis, by regulation of tumorsuppressors (p53) [105] in CM and UM [106,107,108]. |
| miR-21 [98] | Not DE between monosomy and disomy 3 | Plasma | RT-PCR | |
| miR-34a [94] | Upregulated in UM-patients |
EVs: vitreous and FFPE UM-Tissue | TLDA | PDL-1 is regulated by p53 via miR-34, causing immune evasion: UL16-binding protein 2 (ULBP2) is downregulated causing a diminished cell recognition by NK-cells [109,110]. |
| miR-92b [98] | Upregulated in monosomy 3 | Plasma | RT-PCR | Promotes proliferation and migration in hepatocellular carcinoma. No mechanistic information is known in (U)M [111]. |
| miR-107 [88] | Upregulated in UM-patients |
EVs: isolated liver perfusate |
RT2 array | Inhibits cell proliferation, migration, and invasion in CM. Highest expression is seen in metastatic melanoma [112]. |
| miR-124 [88] | Upregulated in UM-patients |
EVs: isolated liver perfusate |
RT2 array | Homeobox 11 (HOXA11)-antisense RNA promotes proliferation and invasion by inhibiting miR-124 in UM [113]. MiR-124 inhibits proliferation, migration, invasion and promotes apoptosis of melanoma cells [114]. |
| miR-125b [97] | Upregulated in metastatic disease |
Plasma | RT-PCR | Induces apoptosis and inhibits proliferation and migration of CM cell line cells by targeting neural cell adhesion molecules (NCAM) [115]. |
| miR-146a [94,97] | Upregulated in UM-patients |
EVs: vitreous, plasma and FFPE UM-Tissue; Plasma |
TLDA/ RT-PCR |
MiR-146 has a potential immunosuppressive role, when upregulated it causes NK-cell proliferation inhibition and apoptosis induction [103]. Additionally, miR-146 is regulated by microphtalmia-associated transcription factor (MITF) [94]. |
| miR-146a [97] | Upregulated in metastatic patients | Plasma | RT-PCR | |
| miR-155 [97] | Upregulated in metastatic patients |
Plasma | RT-PCR | Is upregulated in UM-tumors and promotes invasion and proliferation by targeting Nedd4-family interactive protein 1 (NDFIP1). NDFIP1 is necessary for ubiquitination and translocation of, tumor suppressor, PTEN [116,117,118]. Upregulation is correlated to monosomy 3 status [118]. |
| miR-155 [94] | Downregulated in UM-patients | VH and VH EVs | TLDA | |
| miR-181a [97] | Downregulated in metastatic patients |
Plasma | RT-PCR | Upregulation inhibits CTD small phosphatase like (CTDSPL) expression, which in turn promotes cell cycle progression in UM cells [119]. |
| miR-181a [94] | Downregulated in UM-patients | VH and VH EVs | TLDA | |
| miR-181a [97] | Upregulated in UM-patients | Plasma | RT-PCR | |
| miR-210 [88] | Upregulated in UM-patients |
EVs: isolated liver perfusate |
RT2 array | Targets vascular endothelial growth factor (VEGF)-dependent endothelial cell migration and tube formation factor ephrin A3 and subsequently promotes angiogenesis by formation of capillary like structures [120] and is induced by hypoxia in melanoma [121]. |
| miR-223 [98] | Upregulated in monosomy 3 | Plasma | RT-PCR/ qNPA |
Regulates and suppresses myeloid derived suppressor cells, which expand during pathology and are related to UM [122,123,124]. |
| miR-223 [97] | Upregulated in UM and metastatic patients | Plasma | RT-PCR | |
| miR-320a [88] | Upregulated in UM-patients |
EVs: isolated liver perfusate |
RT2 array | Inhibits the epithelial to mesenchymal transition (EMT) by regulating the transforming growth factor (TGF)-β1/suppressor of mothers against decapentaplegic (SMAD) pathway [125,126]. |
| miR-370 [88] | Upregulated in UM-patients |
EVs: isolated liver perfusate |
RT2 array | Overexpression promotes cell growth and invasion of melanoma cells by regulation of pyruvate dehydrogenase E1 subunit Beta (PDHB) [127]. |
| miR-486a-5p [88] | Upregulated in UM-patients |
EVs: isolated liver perfusate |
RT2 array | Overexpression inhibits proliferation and migration in hepatocellular [128] and colorectal cancer [129]; however, no mechanistic information is available for (U)M. |