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Cancer Res. 2014 Mar 15;74(6):1801-13. doi: 10.1158/0008-5472.CAN-13-3311-T. Epub 2014 Mar 5.

miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9 pathway.

Author information

1
Authors' Affiliations: Department of Medical Oncology; Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute; Harvard School of Public Health; Department of Pathology, Brigham & Women's Hospital; Department of Developmental Biology, Harvard School of Dental Medicine; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and Experimental Therapies, H. Lee Moffitt Cancer Center, Florida; and Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, China.

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.

PMID:
24599134
PMCID:
PMC3959627
DOI:
10.1158/0008-5472.CAN-13-3311-T
[Indexed for MEDLINE]
Free PMC Article

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