MiRNA-29b suppresses tumor growth through simultaneously inhibiting angiogenesis and tumorigenesis by targeting Akt3

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.

Keywords: Akt3; Angiogenesis; Breast cancer; miR-29b.