miR-30-5p functions as a tumor suppressor by targeting BCL9

Deregulated Wnt/b-catenin signaling underlies the pathogenesis of a broad range of human cancers including multiple myeloma (MM). Thus, the b-catenin transcriptional complex has emerged as a high-priority pharmacologic target. The BCL9 oncogene is a critical transcriptional co-activator of b-catenin, and studies from our laboratory have implicated this transcriptional complex in MM disease initiation and progression. Micro RNAs regulate the expression of oncogenes and tumor suppressor genes, and because they play important roles as biologic inhibitors of cancer growth, they have great potential as novel therapeutic agents. Here we provide evidence for a role of miR-30s family in regulating expression of BCL9 and as a novel therapeutic agent in MM. Ectopic expression of miR-30s and shBCL9 were associated with decreased expression of BCL9, Wnt reporter activity, and expression of Wnt downstream target genes, as well as inhibition of proliferation and migration and promotion of apoptosis of MM cells.