<p>PDF file - 179KB, Sequence of oligonucleotides used in this study.</p>

<p>PDF file - 2673KB, MiR-30s target BCL9 in MM cells.</p>

PDF file - 141KB

PDF file - 2071KB, MiR-30s treatment does not have a negative impact on bone disease in MM1S-Luc-Neo bearing mice.

<p>PDF file - 2673KB, MiR-30s target BCL9 in MM cells.</p>

<p>PDF file - 1007KB, Knockdown expression of miR-30s enhances BCL9 expression in MM cells.</p>

<p>PDF file - 1392KB, BMSCs decrease miR-30s levels, and enforced expression of miR-30s inhibits CAM-DR in MM cells.</p>

<p>PDF file - 1007KB, Knockdown expression of miR-30s enhances BCL9 expression in MM cells.</p>

PDF file - 179KB, Sequence of oligonucleotides used in this study.

Abstract Wnt/β-catenin signaling underlies the pathogenesis of a broad range of human cancers, including the deadly plasma cell cancer multiple myeloma. In this study, we report that downregulation of the tumor suppressor microRNA miR-30-5p is a frequent pathogenetic event in multiple myeloma. Evidence was developed that miR-30-5p downregulation occurs as a result of interaction between multiple myeloma cells and bone marrow stromal cells, which in turn enhances expression of BCL9, a transcriptional coactivator of the Wnt signaling pathway known to promote multiple myeloma cell proliferation, survival, migration, drug resistance, and formation of multiple myeloma cancer stem cells. The potential for clinical translation of strategies to re-express miR-30-5p as a therapeutic approach was further encouraged by the capacity of miR-30c and miR-30 mix to reduce tumor burden and metastatic potential in vivo in three murine xenograft models of human multiple myeloma without adversely affecting associated bone disease. Together, our findings offer a preclinical rationale to explore miR-30-5p delivery as an effective therapeutic strategy to eradicate multiple myeloma cells in vivo. Cancer Res; 74(6); 1801–13. ©2014 AACR.