BAVM may occur because of pressure and damage to blood vessel tissue. With the weakening of the vessel walls, the vessel structure changes, and blood may leak into the brain or surrounding tissues. The treatment of BAVM includes open surgery, interventional therapy and radiotherapy, but for large and high Spetzler-grade BAVM, few treatments are available. It is indeed needed to get clear how BAVMs generate and develop. Matrix metalloproteinases are a family of zincdependent proteolytic enzymes that degrade ECM and basement membrane barriers to remodel and maintain the pericellular environment, which may result in the destabilization of vessels and lead to angiogenesis. MMPs are dyregulated in almost every human cancer. It has been reported to release cell surface molecules, including E-cadherin, promote mammary carcinogenesis and is related to several diseases that are AbMole Gemifloxacin mesylate characterized by unstable vascular and matrix scaffolds. In this study, we found that the expression of MMP3 increased in vessel endothelial cells and adventitia in BAVM tissues by immunohistochemical staining, which implies that the overexpression of MMP3 affects the tumorigenesis of BAVM. Further, we detected differential transcriptional activity of the MMP3 promoter caused by 2709 AbMole Folic acid polymorphism, finding that the minor allele G induced a lower transcriptional activity and lead to a decreased expression of MMP3 than did the major allele A. This result is consistent with our previous finding in an epidemiology case-control study that variant allele 2709G was significantly associated with a decreased risk of developing BAVM. The overexpression of MMP3 may be a risk factor for BAVM tumorigenesis, while decreased MMP3 expression could be a protective factor. The risk of tumor development conferred by the A allele has been reported in several different types of cancers and in different ethnic populations. In addition to its association with BAVM mentioned above, the A allele was also found to increase the incidence of gliomas, esophageal carcinoma and lung cancer in the Chinese Han population. Moreover, in US datasets, rs522616A was identified as an ovarian cancer susceptibility “hot-spot” and was significantly related to the development of chronic periodontitis. However, all of these results were reported in simple gene association studies, and none provided any experimental evidence of the effects of this allele. The findings presented in this study offer a mechanistic explanation for the risk presented by 2709A and provide molecular evidence that the SNP in MMP3 contributes to the etiology of BAVM. Furthermore, we clarified how the 2709A allele of the MMP3 promoter up-regulated the gene expression. Bioinformatics analyses suggested that the transcription factor C-MYB might bind to the promoter containing the A allele allele but not containing the G allele, and it was confirmed to bind to the SNP region both in cell lines and in AVM samples in vivo. As c-myb is a famous oncogene that is overexpressed in most cancers or pretumorous cells, our finding that c-myb increased the expression driven by the A allele promoter but not the G allele promoter implies that c-myb may be one important factor that interacts with rs522616 to regulate the MMP3 expression. In particular, C/EBP, has a target sequence within this region and it is a CCAAT enhancer factor, which may help elevate the gene expression. C/EBP is also thought to be related to tumor invasion and migration.