MicroRNAs: Novel Crossroads between Myeloma Cells and the Bone Marrow Microenvironment

Table 1

miRNAs acting in the context of the BMM.

miRNA	Expression pattern	Function in MM-BMM	Target	Reference
miR-15a/-16	Downregulated in MM cells	Tumor suppressors in MM cells, reduce growth and migration of MM and ECs and secretion of VEGF in MM cells	AKT3	[21, 80, 81, 83]
miR-29b	Downregulated in MM cells	Reduces growth and induces apoptosis in MM cells; regulates osteoclast differentiation	MCL-1, CDK6,; C-FOS, MMP2, and NAFTc-1	[22, 106]
miR-30c	Downregulated in MM cells	Tumor suppressor miRNA, inhibits growth and survival of MM cells	BCL9	[96]
miR-34a	Downregulated in MM cells	Induces growth inhibition and apoptosis in MM cells	BCL2, CDK6, and NOTCH1	[25]
miR-125b	Downregulated in MM cells	Tumor suppressor miRNA inhibits growth and survival of MM cells	IRF-4; BLIMP-1	[23]
miR-145	Downregulated in MM cells	Regulates angiogenesis	ANGPTL1	[125]
miR-199a	Downregulated MM cells after hypoxia; Downregulated in BM-MSCs	Induces osteogenesis, reduces MM and ECs migration, and increases adhesion to BMSCs	HIF-1α; MAPK Semaphorin	[23, 110]
Let-7 family	Downregulated in MM cells	Regulates VEGF level promoting angiogenesis	HIF-3α	[125]
miR-21	Upregulated in BMSCs after MM contact, upregulated in MM cells	Affects RANK-L/OPG ratio in MM-BMSCs cocultures; oncomiR in MM cells, increases growth, survival, and clonogenicity	OPG; PTEN	[28, 29]
miR-92a	Upregulated in MM cells	Regulates VEGF level promoting angiogenesis	VEGF	[125]
miR-125a-5p	Upregulated in MM cells	Induces growth and migration and inhibits apoptosis of MM cells	P53	[30]
miR-135b	Upregulated in MM BMSCs	Inhibits osteogenesis	SMAD5	[107]