Table 1. Compilation of miRNAs associated with angiogenesis.
miRNA | Cell type | miRNA target(s) (direct or indirect*) | Function (by miRNA overexpression or inhibition) and putative role in angiogenesis | References |
---|---|---|---|---|
miR-221 miR-222 |
EC (HUVECs, EAhy 296) Prostate cancer cell lines |
c-kit, eNOS* p27/Kip1 |
Overexpression reduces tube formation, migration and wound healing (scratch assay) in response to SCF. ↓EC-mediated angiogenesis Induce proliferation and cell cycle progression. Inhibition reduces proliferation, increase p27 and reduces clonogenity of cells. ↑Tumor induced angiogenesis |
18, 19 84 |
let-7f miR-27b |
EC (HUVECs) | ND | Inhibition reduces in vitro sprout formation ↑EC-mediated angiogenesis |
16 |
miR-126 | EC (HUVECs, HAEC, mouse ECs) | Spred-1, PIK3R2/p85-β, VCAM-1 | Inhibition increases TNF-induced expressionof VCAM-1 and leukocyte adhesion to ECs Regulates vascular integrity and angiogenesis in miR-126 knockdow zebrafish and miR-126-/- mice. Inhibition reduces tube formation, sprout formation, wound healing (scratch assay) and proliferation in response to VEGF and FGF. ↑EC-mediated angiogenesis |
17, 22, 85 |
miR-130a | EC (HUVECs) | GAX, HOXA5 | Overexpression antagonized the inhibitory effect of GAX on EC proliferation, migration and tube formation and the inhibitory effects of HoxA5 on tube formation ↑EC-mediated angiogenesis |
107 |
miR-210 | EC (HUVECs) Breast and colon cancer cell lines, nasopharyngeal carcinoma cell line, head and squamous cell carcinoma |
EphrinA3 ND |
Stimulated by hypoxia. Overexpression stimulates tube formation and migration. ↑EC-mediated angiogenesis Stimulated by hypoxia. decrease proapoptotic signaling in a hypoxic environment. ↑Tumor induced angiogenesis |
108 110, 111 |
miR-15 miR-16 |
Nasopharyngeal carcinoma cell line Chronic lymphocytic leukemia (CLL) Colon cancer cells | VEGF, Bcl2 | Downregulated by hypoxia. Overexpression induces apoptosis in leukemic cell line model. Cell cycle regulation. Inhibition reduces number of cells G0/G1 promoting cell cycle progression. ↓Tumor induced angiogenesis |
111, 115, 116 |
miR-378 | Glioblastoma cells | Sufu, Fus-1 | Overexpression promotes cell survival tumur growth and angiogenesis in vivo. ↑Tumor induced angiogenesis | 140 |
miR-17-92 cluster | EC (HUVECs) Malignant lymphoma cells, Colorectal cancer cells, NSCLC Lymphocytes |
Tsp-1 (miR-18a) E2F1 (miR-17-5p / miR-20a) CTGF (miR-18a, Tsp-1 (miR-19) PTEN, Bim |
Stimulated by VEGF. Overexpression promotes cell proliferation and cord formation converse effects by inhibition. ↑EC-mediated angiogenesis Expression control by c-Myc and E2F. Promote cell proliferation and survival. Overexpression in colonocytes form larger and better-perfused tumors in vivo. ↑Tumor induced angiogenesis Overexpression contributes lymphoproliferative disease. |
20 101, 120, 122, 123 127 |
miR-296 | EC (human brain microvascular ECs) | HGS | Stimulated by glioma cells and angiogenic factors (EGF, VEGF). Inhibition reduces tube formation and migration (scratch assay) in vitro and angiogenesis in tumor xenografts in vivo. ↑EC-mediated and tumor induced angiogenesis | 109 |
miR-155 | EC, VSMC, Fibroblast Breast cancer cells, malignant lymphoma cells, NSCLC Lymphocytes, macrophages |
AT1R ND ND |
Inhibtion increases AT1R expression and Ang II-induced ERK1/2 activation. ?EC-mediated angiogenesis Required for normal immune and imflammatory responses |
95, 141 97, 121, 122,142, 143 |
ND= not determined