Crosstalk between microRNA30a/b/c/d/e-5p and the Canonical Wnt Pathway: Implications for Multiple Myeloma therapy

Dysregulation of transcription via the Wnt/beta-catenin signaling pathway underlies the pathogenesis of a wide variety of frequent human cancers. These include epithelial carcinomas such as colorectal cancer and hematologic malignancies such as multiple myeloma. Thus, the Wnt/beta-catenin pathway potentially offers an attractive target for cancer therapy. This approach, however, has thus far proved challenging because the pathway plays a number of critical roles in physiologic homeostasis and because drugs that broadly target the pathway have unacceptable side effects. miRNAs function as regulators of gene expression and have also been implicated in the pathogenesis of multiple myeloma and other human cancers, offering the promise of novel therapeutic approaches if they can be applied effectively in vivo. Because BCL9 is a critical transcriptional coactivator of beta-catenin that is aberrantly expressed in many human cancers but is of low abundance in normal tissues_ENREF_5, the Wnt/beta-catenin/BCL9 complex has emerged as a promising and most likely relatively safe therapeutic target in cancers with dysregulated Wnt/beta-catenin activity. This review discusses recent advances in the biology of Wnt inhibitors and the appealing possibility of a functional link between BCL9 and miRNA30a/b/c/d/e-5p that could be exploited for multiple myeloma therapy. (C)2014 AACR.