Table 2.
Effects of hypoxic miRNAs listed in Figure 1 (red arrowheads) on melanoma progression, metastasis, and therapy resistance. Mt, Metastatic expansion; Pr, Proliferation; Is, Immunosuppression; Dr, Drug resistance; EMT, Epithelial to Mesenchimal Transition; * Refer to Supplementary Materials for the specific reference list.
| miRNA Name | Involved Process | Oncomir | Effects | References * |
|---|---|---|---|---|
| hsa-let-7f-5p | Mt | No | Interferes with cell anchorage and promotes cell cycle process during metastatic expansion |
[116] |
| hsa-mir-10b-5p | Mt | Yes | Promotes progression and metastasis through by donwregulation of ITCH in Wnt/beta-Catenin pathway |
[117] |
| hsa-mir-125a-3p | Mt, Dr | No | Promotes melanoma progression and metastasis via Lin28B protein; Promotes melanoma resistance to the BRAF inhibitor Vemurafenib via suppression of apoptotic pathways |
[118,119] |
| hsa-mir-150-5p | Mt | No | Key regulator of proliferation, invasion and glycogenesis in malignant melanoma through SIX1 |
[120] |
| hsa-mir-152-3p | Mt | No | Promotes malignant melanoma progression by binding to the lncRNA HOTAIR |
[121] |
| hsa-mir-155-5p | Pr | No | Can increase melanoma progression by modulation of the SKI factor | [122] |
| hsa-mir-181b-3p hsa-mir-181b-5p hsa-mir-181d-5p |
Pr | No | Elicit melanoma cell cycle by targeting the CTDSPL protein | [123] |
| hsa-mir-188-3p | Mt | No | Sustains melanoma progression via Mesenchimal Stem Cell reprogramming | [124] |
| hsa-mir-191-3p hsa-mir-191-5p |
Pr | No | Associated with poor survival in melanoma patients | [125] |
| hsa-mir-196a-5p | Pr | No | Aberrantly expressed in melanoma by disregulation of HOX-C8 expression | [126] |
| hsa-mir-199a-3p | Mt | Yes | Promotion of melanoma metastasis and angiogenesis by targeting the ApoE lipoprotein | [127] |
| hsa-mir-200a-3p | Mt, Dr | No | Reduced response to CDK4/6 inhibitor in highly proliferative metastatic melanoma via diminished expression of CDK6 |
[128] |
| hsa-mir-200b-3p | Pr | No | Activates melanoma invasiveness, progression and EMT via the NEAT1/SMAD2 axis | [129] |
| hsa-mir-203a-3p | Mt | Yes | Promotion of stemness, increased BRAF expression and augmented tumorigenesis in melanoma cell lines and in vivo | [130] |
| hsa-mir-210-3p | Is | No | Promotes melanoma progression by hypoxia-induced immunosuppression in oxygen-deprived regions of the melanoma microenvironment favoring the evolution of cancer stem cells and the resistance to drug therapy |
[131] |
| hsa-mir-21-3p | Mt | Yes | Promotes melanoma cell invasiveness by decreasing the expression of the tissue Metalloproteinase 3 inhibitors in vivo Enhances melanoma invasion and metastasis by promoting the insurgence of NRAS and BRAF mutation and by increasing the expression of L1CAM |
[132,133] |
| hsa-mir-21-5p | Pr | Yes | Targets CDKN2C and activates melanoma cell progression and G1/S transition |
[134] |
| hsa-mir-224-5p | Mt | Yes | Induction of EMT by TXNIP downregulation | [135] |
| hsa-mir-24-3p | Mt, Dr | No | Confers resistance to Vemurafenib through the occurrence of BRAF mutations in melanoma |
[136] |
| hsa-mir-26b-5p | Is | No | Elicits melanoma progression by favoring the HLA class I-mediated immune escape | [137] |
| hsa-mir-30a-5p | Dr | No | Confers resistance to Cisplatin by targeting the IGF1R gene | [138] |
| hsa-mir-30d-3p hsa-mir-30d-5p |
Mt, Is | Yes | Enhances melanoma cell invasiveness and immunosuppression (via increasing Treg cells) during metastatic expansion by modulation of GalNAc transferases |
[139] |
| hsa-mir-373-3p | Mt, Is | Yes | Decreases immunovisibility to melanoma thus increasing tumour dissemination; Promotion of melanoma cell invasiveness by SIK1 targeting |
[140,141] |
| hsa-mir-93 | Mt | No | Found upmodulated in melanoma metastases | [142] |