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MiRNA-29b suppresses tumor growth through simultaneously inhibiting angiogenesis and tumorigenesis by targeting Akt3
Yan Li1, Bolei Cai2, Liangliang Shen3
1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
Abstract:
The traditional anti-angiogenic cancer therapy could trigger hypoxia induced factor (HIF) response, leading to "reactive resistance" to chemotherapy. Simultaneously inhibiting both angiogenesis and tumorigenesis would be ideal to overcome this limitation. MicroRNAs (miRNAs) are increasingly explored as new agents for cancer therapy. In the present study, we identified a microRNA (miR-29b) with the ability of simultaneously inhibiting angiogenesis and tumorigenesis. Ectopic expression of miR-29b inhibits HUVECs formed three-dimensional capillary-like tubular structures, tumor cell proliferation, migration and tumor formation. Systemic administration of miR-29b potently suppressed tumor vascularization and cancer cell activity in vivo, resulting in dramatic suppression of tumor growth without toxicity. Moreover, we demonstrated the role of miR-29b in anti-angiogenesis and anti-tumorigenesis is through targeting Akt3 and inducing VEGF and C-myc arrest in breast cancer cells. These findings indicate that this single miRNA could be used as an efficient anti-cancer therapeutic agent to address a critical challenge in cancer therapy.
Insights
This study identifies microRNA-29b (miR-29b) as a novel therapeutic agent. miR-29b simultaneously inhibits angiogenesis and tumor growth, offering a promising strategy to overcome resistance in cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Traditional anti-angiogenic cancer therapy can induce hypoxia-induced factor (HIF) response, leading to reactive resistance.
- Simultaneous inhibition of angiogenesis and tumorigenesis is crucial for effective cancer treatment.
- MicroRNAs (miRNAs) are emerging as potent therapeutic agents in oncology.
Purpose of the Study:
- To identify a microRNA capable of simultaneously inhibiting angiogenesis and tumorigenesis.
- To evaluate the therapeutic potential of miR-29b in preclinical cancer models.
- To elucidate the molecular mechanisms underlying miR-29b's anti-cancer effects.
Main Methods:
- Ectopic expression of miR-29b in cancer cells and endothelial cells.
- In vitro assays for angiogenesis, cell proliferation, and migration.
- In vivo studies involving systemic administration of miR-29b in tumor-bearing mice.
- Molecular analysis to identify miR-29b targets (Akt3, VEGF, C-myc).
Main Results:
- Ectopic miR-29b expression inhibited endothelial cell capillary-like structure formation, tumor cell proliferation, migration, and tumor formation.
- Systemic miR-29b administration suppressed tumor vascularization and cancer cell activity in vivo, leading to significant tumor growth inhibition without toxicity.
- miR-29b targets Akt3 and induces VEGF and C-myc arrest in breast cancer cells, mediating its anti-angiogenic and anti-tumorigenic effects.
Conclusions:
- miR-29b possesses dual activity against angiogenesis and tumorigenesis.
- Systemic delivery of miR-29b demonstrates potent anti-cancer efficacy and a favorable safety profile.
- miR-29b represents a promising single-agent therapeutic strategy for addressing critical challenges in cancer therapy.