Related Experiment Video
Updated: Feb 8, 2026
Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis
Published on: November 14, 2016
Therapeutic Silencing of miR-214 Inhibits Tumor Progression in Multiple Mouse Models
Daniela Dettori1, Francesca Orso2, Elisa Penna1
1Molecular Biotechnology Center (MBC), University of Torino, Torino, Italy; Department Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Abstract:
We previously demonstrated that miR-214 is upregulated in malignant melanomas and triple-negative breast tumors and promotes metastatic dissemination by affecting a complex pathway including the anti-metastatic miR-148b. Importantly, tumor dissemination could be reduced by blocking miR-214 function or increasing miR-148b expression or by simultaneous interventions. Based on this evidence, with the intent to explore the role of miR-214 as a target for therapy, we evaluated the capability of new chemically modified anti-miR-214, R97/R98, to inhibit miR-214 coordinated metastatic traits. Relevantly, when melanoma or breast cancer cells were transfected with R97/R98, anti-miR-214 reduced miR-214 expression and impaired transendothelial migration were observed. Noteworthy, when the same cells were injected in the tail vein of mice, cell extravasation and metastatic nodule formation in lungs were strongly reduced. Thus, suggesting that R97/R98 anti-miR-214 oligonucleotides were able to inhibit tumor cell escaping through the endothelium. More importantly, when R97/R98 anti-miR-214 compounds were systemically delivered to mice carrying melanomas or breast or neuroendocrine pancreatic cancers, a reduced number of circulating tumor cells and lung or lymph node metastasis formation were detected. Similar results were also obtained when AAV8-miR-214 sponges were used in neuroendocrine pancreatic tumors. Based on this evidence, we propose miR-214 as a promising target for anti-metastatic therapies.
Insights
New anti-miR-214 compounds, R97/R98, effectively inhibit melanoma and breast cancer metastasis. Systemic delivery reduced circulating tumor cells and metastasis formation in mice, suggesting miR-214 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- MicroRNA-214 (miR-214) is upregulated in malignant melanomas and triple-negative breast tumors.
- miR-214 promotes tumor metastasis by influencing pathways involving miR-148b.
- Therapeutic strategies targeting miR-214 are being explored to combat cancer spread.
Purpose of the Study:
- To evaluate the efficacy of novel chemically modified anti-miR-214 oligonucleotides (R97/R98) in inhibiting miR-214-driven metastatic traits.
- To assess the therapeutic potential of R97/R98 anti-miR-214 in preclinical models of melanoma, breast, and neuroendocrine pancreatic cancers.
Main Methods:
- Transfection of cancer cells with R97/R98 anti-miR-214 to assess inhibition of miR-214 expression and cell migration.
- In vivo studies involving tail vein injection of transfected cells and systemic delivery of R97/R98 compounds in mouse models.
- Evaluation of circulating tumor cells and metastatic nodule formation in lungs and lymph nodes.
- Utilizing adeno-associated virus serotype 8 (AAV8)-miR-214 sponges in neuroendocrine pancreatic tumor models.
Main Results:
- R97/R98 transfection reduced miR-214 expression and impaired transendothelial migration of melanoma and breast cancer cells.
- In vivo, R97/R98 treatment significantly reduced cell extravasation and lung metastasis formation.
- Systemic delivery of R97/R98 compounds decreased circulating tumor cells and metastasis in multiple cancer types.
- AAV8-miR-214 sponges also demonstrated efficacy in reducing metastasis in neuroendocrine pancreatic tumors.
Conclusions:
- Chemically modified anti-miR-214 oligonucleotides (R97/R98) are effective in inhibiting miR-214-mediated tumor cell metastasis.
- Systemic delivery of these anti-miR-214 agents shows promise for reducing metastasis in various cancers.
- miR-214 represents a promising therapeutic target for developing novel anti-metastatic strategies.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
00:46Feedback Inhibition
01:30Enzyme Inhibition
01:13Therapeutic Index
01:49Multiple Allele Traits
02:34Inhibition of Cdk Activity