MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling

• Published in: Oncogene Vol. 34; no. 15; pp. 1968 - 1978
• Main Authors: Xiao, F, Qiu, H, Cui, H, Ni, X, Li, J, Liao, W, Lu, L, Ding, K
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 09.04.2015
• Subjects: Angiogenesis; Animals; Bone Morphogenetic Protein Receptors, Type I - genetics; Bone Morphogenetic Protein Receptors, Type I - metabolism; Bone morphogenetic proteins; Care and treatment; Colon cancer; Colonic Neoplasms - blood supply; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - therapy; Colorectal cancer; DNA-binding protein; Female; Genetic aspects; Growth; HEK293 Cells; Heterografts; HT29 Cells; Humans; Id1 protein; Inhibitor of Differentiation Protein 1 - antagonists & inhibitors; Inhibitor of Differentiation Protein 1 - metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - administration & dosage; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Phosphorylation; Physiological aspects; Polysaccharides; Proteins; Risk factors; Signal Transduction; Smad protein; Smad Proteins - antagonists & inhibitors; Smad Proteins - metabolism; Transfection; Tumor cells; Xenografts; China
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2014.134

The previous studies in this lab discovered that microRNA-885-3p (miR-885-3p) was regulated by a sulfated polysaccharide that bound to bone morphogenetic protein receptor, type IA (BMPR1A) to inhibit angiogenesis. However, its specific role and its mechanism of action in tumor cells have not been elucidated. We show that miR-885-3p markedly suppresses angiogenesis in vitro and in vivo. MiR-885-3p inhibits Smad1/5/8 phosphorylation and downregulates DNA-binding protein inhibitor ID-1 (Id1), a proangiogenic factor, by targeting BMPR1A, leading to impaired angiogenesis. Overexpression or silencing of BMPR1A affects angiogenesis in a Smad/Id1-dependent manner. We further show that miR-885-3p impairs the growth of HT-29 colon cancer cell xenografts in nude mice by suppressing angiogenesis through disruption of BMPR1A and Smad/Id1 signaling. These results support a novel role for miR-885-3p in tumor angiogenesis by targeting BMPR1A, which regulates a proangiogenic factor, and provide new evidence that targeting miRNAs might be an effective therapeutic strategy for improving colon cancer treatment.