In a previous report, Research group lead by Prof. DING Kan, Glycochemistry & Glycobiology lab in Shanghai Institute of Materia Medica (SIMM),CAS isolated a glucan from the well-known Chinese herb Gastrodia elata Bl. The sulfated derivative of this glucan, WSS25, is a new drug candidate with patent granted by China, US, Europe and Japan Patent Bureau. It may disrupt angiogenesis and inhibit xenografted hepatocarcinoma cell growth (J Biol Chem 2010, 285(42):32638-46.). However, the mechanism underlying the regulation of angiogenesis by WSS25 is not well understood.

Prof. DING Kan’s group focuses on intensive study of this polysaccharide involved in angiogenesis. Using genome-wide human microRNA (miRNA) microarray analysis, 38 miRNAs are found to be regulated by WSS25 in human microvascular endothelial cells (HMEC-1), including miR-885-3p. Further studies demonstrate that miR-885-3p directly targets bone morphogenetic protein receptor, type IA (BMPR1A), thus blocking BMP/Smad/Id1 signaling and disrupting angiogenesis, to suppress the growth of xenografted HT-29 colon cancer cells. These data provide novel evidences that miR-885-3p plays an important role in colon cancer tumorigenesis and might also be an effective therapeutic target for improving colon cancer treatment.

The study provides the first demonstration concerning the role of miRNA probed by polysaccharide in mediating angiogenesis. Using WSS25 as a probe, the authors uncover a novel function of miR-885-3p and the mechanism of its action in angiogenesis which may shed light on angiogenesis regulation by miRNA. These findings add to new evidences that WSS25 not only modulates angiogenesis factors, but also influences miRNA function. This study also advances our understanding of the actions of WSS25 in angiogenesis and even provides further insight into potential WSS25-based new drug development in terms of miRNA. The results have been published online on Oncogene, 2014 Jun 2 (doi: 10.1038/onc.2014.134).

The research work was mainly accomplished by Dr. XIAO Fei in this lab. This program is supported by the National Natural Science Foundation of China, the New Drug Creation and Manufacturing Program and the National Science Fund for Distinguished Young Scholars in China.

Full text: http://www.nature.com/onc/journal/vaop/ncurrent/pdf/onc2014134a.pdf