Argonaute2 promotes myeloma angiogenesis by deregulation of microRNAs

Dysregulation of miRNAs expression contributes to cancer cell proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple myeloma development and progression. Argonaute 2 (AGO2) protein, the core component of RNA-induced silencing complex (RISC), can directly bind miRNAs and mediate target mRNAs degradation. Previous study showed that AGO2 knockdown suppressed the growth and tube formation of HUVECs. In current study, the supernatant of AGO2 over-expression MM lines could induce HUVECs migration and accelerated tube formation. Conversely, the supernatant of AGO2 knockdown MM lines could suppress cell migration and tube formation of HUVECs. Moreover, CAM assay also demonstrated AGO2 can drive neovessel formation of MM in vivo. Using miRNAs microarray, we observed that 25 miRNAs were up-regulated and 14 miRNAs were down-regulated by AGO2 protein. Among these AGO2-associated miRNAs, most Let-7 family and two miR-17-92 cluster members (miR-17a and miR-92-1), known as pro-angiogenetic miRNAs, were the dominant positively regulated miRNAs by AGO2, and the anti-angiogenetic miRNAs, such as miR-145 and miR-361 were inversely regulated by AGO2 protein, which play crucial role in AGO2 mediating angiogenesis.