MiR-15a/16 regulates the growth of myeloma cells, angiogenesis and antitumor immunity by inhibiting Bcl-2, VEGF-A and IL-17 expression in multiple myeloma

• The downregulation of miR-15a/16 was correlated with International Staging System (ISS) stage in MM patients.
• miR-15a/16 inhibited myeloma cells proliferation, and increased apoptosis rate of myeloma cells by suppressing Bcl-2.
• miR-15a/16 could inhibit angiogenesis by decreasing VEGF-A in MM.
• miR-15a/16 could enhance antitumor immunity by decreasing IL-17 levels in MM.
• miR-15a/16 may function as a tumor suppressor in MM through multiple regulatory mechanisms.

miRNAs have been reported to be involved in the pathogenesis of many cancers. In this article, we investigated the role and the mechanisms of miR-15a/16 in the pathogenesis of multiple myeloma (MM). We found that miR-15a/16 was down-regulated in bone marrow-derived mononuclear cells (BM-MNCs) of newly diagnosed patients with MM and the downregulation of miR-15a/16 was correlated with International Staging System (ISS) stage. We then demonstrated miR-15a/16 inhibited myeloma cells proliferation, and increased apoptosis rate of U266 cells by suppressing the expression of anti-apoptosis protein Bcl-2. We also found miR-15a/16 could decrease VEGF-A and IL-17 levels in the supernatant of myeloma cells. These results indicate that miR-15a/16 may function as a tumor suppressor in MM through multiple regulatory mechanisms and they may be potential targets for the therapy of MM.