title: 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.
authors.affiliation: State 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Bolei
authors.initials: B
authors.lastname: Cai
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Shen
authors.affiliation: State 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Shukai
authors.initials: S
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Forth Military Medical University, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Jia-Yi Dentistry and Cosmetic Surgery Clinic, Xi'an, 710032, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: mapx@umich.edu.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
authors.affiliation: State 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. Electronic address: jhchen@fmmu.edu.cn.
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C532045:MIRN29a microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt3; Angiogenesis; Breast cancer; miR-29b