Role of microRNA in regulation of myeloma-related angiogenesis and survival

Table 1 Involvement of microRNAs in multiple myeloma cell proliferation and apoptosis

Activator	miRNA reduced	miRNA overexpressed	Target increased	Target decreased	Effect	Ref.
Deletion, other	miR-15a, miR-16		AKT, S6, MAPK, MAP3KIP3 (TAB3)		Increased proliferation and survival	[30]
	miR-30-5p family		BCL9		Increased Wnt/β-catenin activation	[32]
c-Myc (reduced)	miR-17/92 cluster		Bim		Increased apoptosis	[36,40]
Sp-1 (increased)	miR-29b		Sp-1, CDK6, Mcl-1, caspase-3, Rb phosphorylation			[41,42]
	miR-34a, miR-192, miR-194, miR-215		MDM2, IGF-1		Cell proliferation	[34]
		miR-19a/b		SOCS1, Bim	Reduced apoptosis	[36]
		miR-181a/b, miR-32		PCAF	Reduced p53 acetylation	[36]
		miR-221, miR-222		P27Kip1, p57Kip2, PUMA, PTEN	Increased proliferation	[35]
IL-6		miR-21		STAT-3		[37,38]

AKT: Protein kinase B; MAPK: Mitogen-activated protein kinases; MAP3KIP3: Mitogen-activated protein 3 kinase interacting protein 3; BCL9: B-cell lymphoma 9 protein; MDM2: Mouse double minute 2; IGF-1: Insulin-like growth factor 1; SOCS1: Suppressor of cytokine signaling 1; PCAF: P300/CBP-associated factor; PTEN: Phosphatase and tensin homolog; STAT-3: Signal transducer and activator of transcription 3; PUMA: p53 upregulated modulator of apoptosis; IL-6: Interleukin 6.

Table 2 Involvement of microRNAs in the regulation of multiple myeloma-related angiogenesis

	Target increased	Target reduced	Effect (anti-angiogenic)	Effect (pro-angiogenic)	Ref.
miRNA reduced
miR-15a, miR-16, miR-145	VEGF, ERK pathway, AKT pathway		Reduced EC growth, reduced ability to form capillary structures		[30,31,48]
miR-199a-5p	HIF-1α, SIRT-1		Increased expression of VEGF, IL-8, bFGF, CXCL12, MMP-2		[47]
miRNA increased
Let 7 family		Thrombospondin-1, TIMP-1		Inhibiting anti-angiogenic factors	[48]
miR-92-1		Angiopoietin-like protein 1		Inhibit anti-angiogenic protein	[48]
miR-135b		FIH-1		Alleviate HIF-1α inhibition	[45]

VEGF: Vascular endotelial growth factor; ERK: Extracellular signal-regulated kinase; HIF-1α: Hypoxia inducible factor 1 alpha; SIRT-1: Sirtuin 1; FIH-1: Factor inhibiting HIF-1; IL-8: Interleukin-8; bFGF: Basic fibroblast growth factor; MMP: Matrix metalloproteinase.