. 2020 Jan 27;10(2):191. doi: 10.3390/biom10020191

Table 1.

Detailed overview of miRNAs involved in tumor metabolic and angiogenic signaling.

	miRNA	Cellular Function	Target	Signaling Pathway	Cell Line	References
1	miRNA-105	Promote metastasis	ZO-1 (tight junction protein) MXI1	miRNA based metastasis MYC pathway	MDA-MB-231	[61,62,63,64]
2	miRNA-93	EC glycolysis and EC proliferation	KLF2 and PFKFB3 (in glycolysis). FOXO1 and MYC (in proliferation). WNK lysine deficient protein kinase 1 (WNK1) ↓LATS2	Glycolytic pathway and VEGF pathway Enhances angiogenesis and metastasis to the lungs	MT-1 MDA-MB-231 Breast carcinoma specimens.	[25,65]
3	miRNA-10b and miRNA-196b	Produced in response to tumor secreted VEGF and regulate EPC function and angiogenesis	↓HOXD10	HOX pathway	IDC grade III tumors	[66]
4	miRNA-155	Up-regulates glucose transporters and glycolytic enzymes. Associated with poor prognosis and metastasis.	↓VHL	Oncogenic ↑HIF ↑PIK3R1-PDK/AKT-FOXO3a-cMYC axis	TNBC- late-stage (stage III/IV), lymph node metastasis	[67,68]
5	miRNA-4530	Decreases proliferation, induces apoptosis, promotes angiogenesis	↓VASH1 (endogenous angiogenesis inhibitor	Arrest at S/G2	MCF-7 MDA-MB-231 HUVEC	[69]
6	miRNA-153	Response to high glucose Tumor suppressor EMT suppressor Down-regulated in BC	IRE1α-XBP1 ↓MTDH	↓HIF-1α/VEGFA signaling TGF-β-mediated-EMT	MDA-MB-231 HCC1937 Luminal A and B, Basal, HER 2 positive	[70,71]
7	miRNA-205	Enhances chemosensitivity of breast cancer cells to TAC chemotherapy (docetaxol, doxorubicin plus cyclophosphamide)	↓VEGFA and FGF2	Tumor suppressor, ↓PI3/AKT signaling pathway	MCF-7/A02 and CALDOX	[57]
8	miRNA-206	Suppresses glycolysis	↓VEGF PFKFB3	VEGF/MAPK3/SOX9 ↓proliferation and metastasis	MDA-MB-231, MDA-MB-435, and HCC1395	[72,73]
9	miRNA-221/222	Anti-angiogenic Anti-proliferative Increases senescence Response to high glucose	↓eNOS ↓ZEB2 ↓P27	eNOS signaling	Mouse microvascular endothelial cells (MMECs)	[74,75]
10	miRNA-100	Mesenchymal stem cell derived exosomes	↓VEGF	↓mTOR/↓HIF-1/VEGF pathway	MDA-MB-231, MCF-7, T47D, HUVEC BM-MSC	[76]
11	miRNA-29b	Invasion, proliferation and migration	AKT3 SPIN1	AKT3/VEGF/C-myc ↓WNT and AKT	HUVEC MDA-MB-231	[77]
12	miRNA-23a	Up/down-regulated in specific type of cancers. Aerobic glycolysis Anti-angiogenic	↓LDHA and LDHB	Glycolytic pathway miR-23a/↓RUNX2/↓VEGF-A	HUVEC	[78,79]
13	miRNA-23b	Inversely correlated with metastasis	↓PAK2, MLC II Phosphorylation, under the regulation of AP-1, directly target cytoskeleton genes. JAM-C and ZO-2	Both oncogenic and tumor suppressive Cytoskeletal re-organization, migration and metastasis ↑Vascular permeability and EC tube formation	MCF7 MDA-MB-231 HUVEC Xenograft	[80,81,82]
14	miRNA-182	Oncogenic	↓FBXW7	Hypoxia/miRNA 182/↑HIF-1α/VEGFA axis	hy926 MCF-7 ER and PR positive BC	[83]
15	miRNA-497	Down-regulated EMT	↓VEGFR2, ↓VEGF and ↓HIF-1α ↓ Slug	VEGFR2/Raf/ERK/MEK pathway VEGFR2/PI3K/AKT pathway Tumor-suppressor Hypoxia/miR-497/HIF-1α pathway	MCF-7 4T1 Xenograft Invasive ductal breast cancer	[84,85,86]
16	miRNA-140-5p	Tumor suppressor	↓VEGFA, ↓MMP9	Proliferation-↓Ki 67 Angiogenesis- ↓VEGFA Metastasis- ↓MMP-9	MCF-7 MDA-MB-231	[11]
17	miRNA-467	Response to hyperglycemia Tissue specific	↓TSP-1	Pro-angiogenic	EMT6 (mu) C116	[87,88]
18	miRNA-126	Endothelial cell specific	↓VEGFA ↓PIK3R2 ↓SPRED1	VEGF/PI3K/AKT	MCF-7	[89]
19	miRNA-27a	Pro-angiogenic	↑ZBTB10	Autocrine VEGF/RUNX1/miR27a/ZBTB10 signaling loop	MDA-MB-231 BCSLCs (SK-3rd)	[90]
20	miRNA-21	Responsive to glucose level Pro-angiogenic Modulates ROS level Promotes metastasis	↓PTEN and SMAD7 HIF-1α PDCD4, maspin LZTFL1	TGF-β, AKT-, SMAD- and ERK-dependent signaling Oncogenic Decreased apoptosis and increased proliferation Metastasis and invasion	MCF-7 MDA-MB-231	[91,92,93,94,95,96,97,98]
21	miRNA-503	Anti-angiogenic	↓CCND1	Tumor suppressor ↓FGF2 and VEGFA (hepato cellular carcinoma) Down-regulated in BC tissue	MCF-7, T47D, MDA-MB231, BT549, SKBR3, ZR-75-30	[99,100]
22	miRNA-34a	Response to high glucose	↓SIRT1	Suppress proliferation and invasion by targeting Notch Inhibits BC stemness Tumor-suppressive role	BT-474, MDA-MB-231, MDA-MB-435, MDA-MB-468, SK-BR-3, EC	[101,102,103]
23	miRNA-26a	↓ VEGF dependent migration and proliferation Anti-angiogenic	↓NgBR MCL-1	VEGF/NgBR/↓eNOS pathway Tumor suppresor	HUVECs MDA-MB-231, MCF-7, MDA-MB-435, MDA-MB-468	[104,105]
24	miRNA- 98	Anti-angiogenic	↓MMP11, ↓ALK4	Inhibits cell spreading, cell invasion and tubule formation. Suppress proliferation and survival of BC cells	4T1, MT1, MDA-MB-231, MDA-MB-468, Xenograft	[106]
25	miRNA-126	Response to high glucose ↓Type 2 diabetes	↓VEGFA and PI3K regulatory subunit 2 (PIK3R2) CD97, GPCR	VEGF/PI3K/AKT Tumor suppressor EC migration and tumor angiogenesis	MDA-MB-231 MCF-7 plasma from DM patients	[59,60,107]
26	miRNA-145	Anti-angiogenic	N-RAS and VEGF-A IGF-I/IRS	PI3/AKT/mTOR/p70S6K1 Tumor suppressor Suppressed the invasion and tube formation in EC IRS1/N-RAS/VEGF pathway	MCF-7 MDA-MB-231	[108]
27	miRNA-20a	Predominantly in TNBC pro-angiogenic	↑VEGFA and HIF-1α	VEGFA dependent angiogenesis	MCF-7 MDA-MB-231	[109]
28	miRNA-526b miRNA-655	Tumor associated angiogenesis and lymphangiogenesis	EP4, ↓PTEN and PI3K/Akt ↑VEGFA	PI3K/AKT pathway	MCF-7 ER and PR positive HER 2 negative BC	[46]
29	let-7a	Regulates key anabolic enzymes ROS production	Stearol Co-A Desaturase (SCD) G6PD, FASN, BACH1	Glycolytic pathway OXPHOS pathway Sensitizes BC to doxorubicin	MDA-MB-231	[110]