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Updated: Jan 31, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA-8073: Tumor suppressor and potential therapeutic treatment
Atsuko Mizoguchi1, Aiko Takayama1, Taiga Arai1
1New Frontiers Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
Abstract:
The comprehensive screening of intracellular and extracellular microRNAs was performed to identify novel tumor suppressors. We found that miR-8073 was present in exosome and predominantly exported from colorectal cancer cells. Treatment with a synthetic miR-8073 mimic resulted in a dramatic decrease in the proliferation of various types of cancer cells, which was not observed in similarly treated normal cells. As little is known about the biological functions of miR-8073, its target mRNAs were analyzed by both mRNA expression and in silico sequence analyses, leading to five probable target candidates (FOXM1, MBD3, CCND1, KLK10, and CASP2) that enhance survival during the regulation of the cell cycle, cell proliferation, and apoptosis. We experimentally confirmed that miR-8073 binds the 3'-UTR of each of these mRNA target candidates and that the introduction of a synthetic miR-8073 mimic into cancer cells reduced levels of protein expression. Finally, the antiproliferative effects of miR-8073 were validated in vivo: the subcutaneous injection of a synthetic miR-8073 mimic suppressed colorectal tumor volume to 43% in tumor-bearing xenografted mice. These results suggest that because miR-8073 binds, and thus reduces the levels of, these oncogenic targets, cancer cells must actively downregulate miR-8073 as a survival mechanism. The introduction of miR-8073 into tumors could thus inhibit tumor growth, indicating its great potential for cancer therapeutics.
Insights
MicroRNA-8073 (miR-8073), found in exosomes from colorectal cancer cells, significantly inhibits cancer cell proliferation. Restoring miR-8073 levels offers potential for novel cancer therapeutics.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play crucial roles in cellular processes.
- Dysregulation of miRNAs is implicated in cancer development.
- Identifying novel tumor-suppressive miRNAs is essential for therapeutic strategies.
Purpose of the Study:
- To identify and characterize novel tumor suppressors among intracellular and extracellular miRNAs.
- To investigate the role of miR-8073 in colorectal cancer and other cancer types.
- To explore the therapeutic potential of miR-8073 in cancer treatment.
Main Methods:
- Comprehensive screening of miRNAs in exosomes.
- In vitro proliferation assays using synthetic miR-8073 mimics.
- mRNA expression analysis and in silico target prediction.
- Experimental validation of miRNA-mRNA interactions (3'-UTR binding).
- In vivo tumor xenograft models in mice.
Main Results:
- miR-8073 was identified as an exosomal miRNA predominantly exported from colorectal cancer cells.
- Synthetic miR-8073 significantly reduced proliferation in various cancer cell lines but not normal cells.
- Five target mRNAs (FOXM1, MBD3, CCND1, KLK10, CASP2) involved in cell survival pathways were validated.
- miR-8073 introduction decreased protein expression of validated targets.
- In vivo studies showed miR-8073 suppressed colorectal tumor growth by 43%.
Conclusions:
- miR-8073 acts as a tumor suppressor by targeting oncogenic mRNAs.
- Cancer cells downregulate miR-8073 as a survival mechanism.
- Restoration of miR-8073 holds significant therapeutic potential for inhibiting tumor growth.
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