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Published on: December 13, 2018
Crosstalk between microRNA30a/b/c/d/e-5p and the canonical Wnt pathway: implications for multiple myeloma therapy
Jian-Jun Zhao1, Ruben D Carrasco2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Abstract:
Dysregulation of transcription via the Wnt/β-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/β-catenin in 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, [corrected] 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 β-catenin that is aberrantly expressed in many human cancers but is of low abundance in normal tissues, [corrected] the Wnt/β-catenin/BCL9 complex has emerged as a promising and most likely relatively safe therapeutic target in cancers with dysregulated Wnt/β-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.
Insights
Targeting the Wnt/β-catenin/BCL9 complex offers a promising cancer therapy strategy. This approach may be safer than broad pathway inhibition, especially for multiple myeloma, by focusing on aberrant BCL9 expression.
Area of Science:
- Oncology
- Molecular Biology
- Signaling Pathways
Background:
- Wnt/β-catenin signaling pathway dysregulation drives many human cancers, including colorectal cancer and multiple myeloma.
- Targeting this pathway is attractive for cancer therapy but challenging due to its role in homeostasis and side effects of broad inhibitors.
- MicroRNAs (miRNAs) regulate gene expression and are implicated in cancer pathogenesis, offering potential therapeutic avenues.
Purpose of the Study:
- To review advances in Wnt pathway inhibitors.
- To explore the Wnt/β-catenin/BCL9 complex as a targeted cancer therapy.
- To discuss a potential link between BCL9 and miRNA30a/b/c/d/e-5p for multiple myeloma treatment.
Main Methods:
- Literature review of Wnt pathway biology and inhibitors.
- Analysis of BCL9's role as a transcriptional coactivator of β-catenin.
- Discussion of miRNA involvement in cancer and potential therapeutic exploitation.
Main Results:
- BCL9 is aberrantly expressed in many cancers but scarce in normal tissues, making the Wnt/β-catenin/BCL9 complex a selective therapeutic target.
- Dysregulated Wnt/β-catenin activity is a hallmark of various cancers.
- A functional link between BCL9 and miRNA30a/b/c/d/e-5p may exist for therapeutic applications.
Conclusions:
- The Wnt/β-catenin/BCL9 complex represents a promising and potentially safer therapeutic target for cancers with aberrant Wnt pathway activity.
- Targeting BCL9 offers a more specific approach compared to broad Wnt pathway inhibitors.
- Further research into the BCL9 and miRNA30a/b/c/d/e-5p interaction could yield novel therapies for multiple myeloma.
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