Table 2.
Summary of anti-angiogenic miRNAs involved in tumor angiogenesis regulation.
| miRNAs | Targets | Tumor | Function | References |
|---|---|---|---|---|
| miR-221/222 | c-Kit VEGFR-2 ETS-1 PIK3R1 CDKN1B ZEB2 STAT5A | Metastatic renal cell carcinoma, breast cancer | ↓ endothelial cell migration, proliferation, and ability to form new capillaries ↓ VEGFR-2 |
[75,76,77,78,79,80,81,82,83] |
| miR-126 | VEGF-A PIK3R2 ADM | Esophageal cancer, breast cancer, cervical cancer | ↓ VEGF/PI3K/AKT signaling ↓ Angiogenesis and microvessel density |
[84,85,86] |
| let-7a | TGFBR3 | Pancreatic cancer, hepatocellular carcinoma | ↓ tube formation and migration of endothelial cells | [87,88,89,90] |
| miR-328 | CD44 | Breast cancer MT1cell line | ↓ endothelial cell activity, tubulogenesis and blood vessel formation | [91] |
| miR-135a | FAK IGF-1/PI3K/Akt pathway | Gastric cancer, non-small cell lung cancer | ↓ VEGF signaling | [92,93] |
| miR-29b | VEGF ERK Akt MMP-2 | endometrial carcinoma, breast cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma | ↓ VEGF expression ↓ MAPK/ERK and PI3K/Akt signaling pathways ↓ MMP-2 expression and VEGFR-2 signaling |
[94,95,96,97] |
| miR-206 | VEGF MAPK3 SOX914-3-3ζ/STAT3/HIF-1α/VEGF signaling c-Met/PI3k/Akt/mTOR signaling | laryngeal squamous cell carcinoma, triple negative breast cancer, non-small cell lung cancer | ↓ VEGF expression ↓ endothelial cell migration and capillary tube formation |
[98,99,100,101] |
| miR-140-5p | VEGF-A | colorectal cancer, glioma, glioblastoma | ↓ VEGF-A/MMP2 signaling | [102,103,104] |
| miR-497 | VEGF-A HIF-1α VEGFR-2 | colorectal cancer, breast cancer; renal carcinoma | ↓ VEGF-A/ERK/MMP-9 signaling ↓ tube formation and branch points ↓ MEK/ERK and p38 MAPK pathways |
[105,106,107] |
| miR-377 | VEGF CD133 Sp1 | esophageal squamous cell carcinoma, glioblastoma | ↓ VEGF | [108,109] |
| miR-218 | RICTOR Angiopoietin-2 ROBO1 | Prostate cancer, gastric cancer | ↓ RICTOR/mTOR/HIF-1/VEGF signaling pathway ↓ endothelial cell sprouting, motility and tube formation |
[110,111,112] |
| miR-134 | VEGF-A VEGFR-1 | osteosarcoma | ↓ VEGF-A/VEGFR-1-AKT signaling | [113] |
Abbreviations: miRNAs: microRNAs; VEGFR-2: vascular endothelial growth factor receptor2; ETS-1: E26 transformation-specific sequence-1; PIK3R1: phosphoinositide-3-kinase regulatory subunit 1; CDKN1B: cyclin-dependent kinase inhibitor 1b; ZEB2: Zinc finger E-box-binding homeobox 2; STAT5A: signal transducer and activator of transcription 5A; VEGF-A: vascular endothelial growth factor-A; PIK3R2: phosphoinositide-3-kinase regulatory subunit 2; ADM: adrenomedullin; AKT: RAC-Alpha Serine/Threonine-Protein Kinase; PI3K: phosphoinositide 3-kinase; TGFBR3: transforming growth factor beta (TGFβ) receptor III; CD: cluster of differentiation; FAK: focal adhesion kinase; MMP-2: matrix metalloproteinase-2; MAPK3: mitogen-activated protein kinase3; SOX9: Sry-type HMG box 9; Sp1: specific protein 1; ERK: extracellular regulated kinase; mTOR: mammalian target of rapamycin; RICTOR: rapamycin-insensitive companion of mammalian target of rapamycin; ROBO1: roundabout guidance receptor 1; ↓: down-regulation.