Regulus Therapeutics and Collaborators Discover Role of microRNA in Tumor Angiogenesis
News Nov 07, 2008
Regulus Therapeutics LLC has announced the publication of new research findings in the journal Cancer Cell demonstrating a key role of microRNAs in regulating angiogenesis pathways in cancer, specifically in malignant brain tumors.
Angiogenesis is a physiological process required for the growth and spread of many cancers and the new findings demonstrated that miR-296 is a significant regulator of this pathway. Further, targeting miR-296 with anti-miR-296 antisense oligonucleotides (also called antagomirs) blocked angiogenesis in tumor xenograft models in mice.
This new research was led by Thomas Wuerdinger affiliated with Xandra O. Breakefield’s laboratory at Massachusetts General Hospital and VU Medical Center in Amsterdam, working in collaboration with researchers from Regulus, Anna M. Krichevsky’s laboratory at Brigham and Women’s Hospital, and Ludwig-Maximilians-University in Munich.
“This new research adds to a rapidly growing body of evidence suggesting that microRNAs control important biological pathways and that inhibiting the function of a single microRNA could have a profound effect on disease pathophysiology,” said Peter Linsley, Ph.D., Chief Scientific Officer of Regulus Therapeutics. “The current study shows that miR-296 is a significant regulator of tumor induced angiogenesis, and that anti-miR-296 may thus represent a novel anti-cancer strategy.”
The new paper describes the role of endothelial cell-expressed miR-296 in regulating the formation of new blood vessels. During neovascularization, increased expression of miR-296 represses hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), which in turn regulates additional growth factor receptors, VEGFR and PDGFR. By inhibiting miR-296 with an anti-miR, levels of the growth factor receptors were decreased resulting in decreased growth of blood vessels.
The induction of miR-296 expression was observed in tumor blood vessels isolated from human glioblastoma tumors, suggesting an important role for miR-296 in tumor progression and metastatic potential. The data showed that the regulation of miR-296 in human endothelial cells directly resulted in the modulation of angiogenesis in vitro.
Additionally, the specific inhibition of miR-296 in an in vivo tumor xenograft model resulted in decreased neovascularization of tumors.
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