Antiangiogenic Effect of Alkaloids

Table 1

Effect of different microRNAs on the angiogenic process.

MiRNA	Target gene	Role	Function	Reference
MiR-34a	Silent information regulator 1 (Sirt1)	MiR-34a has been found to target silent information regulator 1 (Sirt1), leading to cell cycle arrest or apoptosis	Antiangiogenesis	[67]
MiR-107	HIF-1β	MiR-107 decreases hypoxia signaling by suppressing expression HIF-1β	Antiangiogenesis	[75]
MiR-132	p120RasGAP	MiR-132 acts as an angiogenic switch by targeting p120RasGAP in the endothelium and thereby inducing neovascularization	Angiogenesis	[76]
MiR-424	Cullin 2 (CUL2)	MiR-424 targeted Cullin 2 (CUL2), a scaffolding protein critical to the assembly of the ubiquitin ligase system, thereby stabilizing HIF-α isoforms	Angiogenesis	[77]
MiR-93	Integrin-β8	MiR-93 promotes angiogenesis by suppressing integrin-β8 expression	Angiogenesis	[71]
MiR-29b	MMP-2	MiR-29b exerted its antiangiogenesis function, at least partly, by suppressing MMP-2 expression in tumor cells	Antiangiogenesis	[78]
MiR-519c	HIF-1α	Overexpression of miR-519c resulted in a significant decrease of HIF-1α protein levels and reduced the tube formation of human umbilical vein endothelial cells	Antiangiogenesis	[79]
MiR-210	VEGF and VEGFR	Overexpression of miR-210 enhances VEGF and VEGFR2 expression and promotes angiogenesis	Angiogenesis	[80]
MiR-155	Von Hippel-Lindau (VHL)	MiR-155 has a pivotal role in tumor angiogenesis by downregulation of VHL	Angiogenesis	[81]
MiR-195	VEGF, VAV2, CDC42	MiR-195 directly inhibited the expression of the proangiogenic factor VEGF and the prometastatic factors VAV2 and CDC42	Antiangiogenesis	[82]
MiR-145	HIF-2α	MiR-145 suppresses HIF-2α expression, thus inhibiting the angiogenesis	Antiangiogenesis	[83]
MiR-26a	HGF-hepatocyte growth factor receptor (cMet)	MiR-26a exerted its antiangiogenesis function, at least in part, by inhibiting HGF-hepatocyte growth factor (cMet) and its downstream signaling pathway	Antiangiogenesis	[84]
MiR-214	Hepatoma-derived growth factor (HDGF)	Downregulation of miR-214 contributes to the unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis	Antiangiogenesis	[85]
MiRNA-24	eNOS	Inhibition of microRNA-24 improves reparative angiogenesis in myocardial infarction	Antiangiogenesis	[86]
MiR-29a	Phosphatase and tensin homolog (PTEN)	TGF-β-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity	Angiogenesis	[87]
MiR-27b	Vascular endothelial growth factor C (VEGFC)	MiRNA-27b targets vascular endothelial growth factor C to inhibit angiogenesis in colorectal cancer	Antiangiogenesis	[88]
MiR-503	FGF2 and VEGF-A	Demonstrate the antiangiogenesis role of miR-503 in tumorigenesis and provide a novel mechanism for hypoxia-induced FGF2 and VEGF-A through HIF1α-mediated inhibition of miR-503	Antiangiogenesis	[89]
MiR-143	Insulin-like growth factor-I receptor (IGF-IR)	Overexpression of miR-143 inhibited cell proliferation, migration, tumor growth, and angiogenesis and increased chemosensitivity to oxaliplatin treatment in an IGF-IR-dependent manner	Antiangiogenesis	[90]
MiR-382	Phosphatase and tensin homolog (PTEN)	MiR-382 induced by hypoxia promotes angiogenesis and acts as an angiogenic oncogene by repressing PTEN	Angiogenesis	[91]
MiR-210	Vascular endothelial growth factor (VEGF)	MiR-210 is a key factor at the microRNA level in promoting angiogenesis and neurogenesis, which was associated with local increased vascular endothelial growth factor (VEGF) levels	Angiogenesis	[92]
MiR-542-3p	Angiopoietin-2 (Angpt2)	MiR-542-3p inhibited translation of Angpt2 mRNA by binding to its 3 UTR, and the addition of miR-542-3p to cultured endothelial cells attenuated angiogenesis	Antiangiogenesis	[93]
MiR-214	Quaking	MiR-214 directly targets Quaking, a protein critical for vascular development. Quaking knockdown reduced proangiogenic growth factor expression and inhibited endothelial cell sprouting similar to miR-214 overexpression	Antiangiogenesis	[94]
MiR-20a	p300	P300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a	Antiangiogenesis	[95]
MiR-15a	FGF2 and VEGF	MiR-15a negatively regulates angiogenesis in vivo and in vitro by suppression of FGF2 and VEGF	Antiangiogenesis	[96]