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Updated: May 2, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9
Jian-Jun Zhao1, Jianhong Lin, Di Zhu
1Authors' 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.
Insights
Downregulation of microRNA miR-30-5p promotes multiple myeloma. Restoring miR-30-5p levels reduced tumor growth and spread in preclinical models, suggesting a potential new therapy for this deadly cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wnt/β-catenin signaling is crucial in multiple myeloma pathogenesis.
- MicroRNAs (miRNAs) play significant roles in cancer development.
- Tumor suppressor miRNAs can be dysregulated in cancer.
Purpose of the Study:
- To investigate the role of miR-30-5p in multiple myeloma.
- To explore the mechanism of miR-30-5p downregulation.
- To evaluate miR-30-5p restoration as a therapeutic strategy.
Main Methods:
- Analysis of miR-30-5p levels in multiple myeloma.
- Investigating the interaction between myeloma cells and bone marrow stromal cells.
- In vivo studies using murine xenograft models of multiple myeloma.
Main Results:
- Downregulation of miR-30-5p is a common event in multiple myeloma.
- Myeloma cell and stromal cell interaction leads to miR-30-5p downregulation.
- BCL9 expression is increased by miR-30-5p downregulation, promoting myeloma progression.
- Restoration of miR-30-5p reduced tumor burden and metastasis in vivo.
- Therapeutic strategies did not adversely affect bone disease.
Conclusions:
- miR-30-5p downregulation is a key event in multiple myeloma.
- Targeting miR-30-5p offers a promising therapeutic avenue.
- miR-30-5p delivery warrants further investigation for multiple myeloma treatment.
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