Angiogenesis is a process of development and growth of new capillary blood vessels from pre-existing vessels. Angiogenic growth factors play important roles in the development and maintenance of some malignancies, of which vascular endothelial growth factor (VEGF)/VEGFR2 interactions are involved in proliferation, migration, and survival of many cancer cells. The aim of this study was to investigate the function of VEGFR2 in human hemangiomas (HAs). Using immunohistochemistry assay, we examined the expression levels of VEGF, VEGFR2, Ki-67, glucose transporter-1 (Glut-1), phosphorylated protein kinase B (p-AKT) and p-ERK in different phases of human HAs. Positive expression of VEGF, VEGFR2, Ki-67, Glut-1, p-AKT and p-ERK was significantly increased in proliferating phase HAs, while decreased in involuting phase HAs (P=0.001; P=0.003). In contrast, cell apoptotic indexes were decreased in proliferating phase HAs, but increased in involuting phase HAs (P<0.01). Furthermore, we used small hairpin RNA (shRNA)-mediated VEGFR2 knockdown in primary HA-derived endothelial cells (HemECs) to understand the role of VEGF/VEGFR2 signaling. Knockdown of VEGFR2 by Lv-shVEGFR2 inhibited cell viability and induced apoptosis in primary HemECs companied with decreased expression of p-AKT, p-ERK, p-p38MAPK and Ki-67 and increased expression of caspase-3 (CAS-3); Overexpression of VEGFR2 promoted cell viability and blocked apoptosis in Lv-VEGFR2-transfected HemECs. Taken together, our findings demonstrate that, increased expression of VEGFR2 is involved in the development of primary HemECs possibly through regulation of the AKT and ERK pathways, suggesting that VEGFR2 may be a potential therapeutic target for HAs.

MicroRNAs (miRNAs) are involved in the gastric carcinogenesis and progression. Here, we confirmed that miR-483 was frequently decreased in gastric cancer patients. The expression levels of miR-483 were negatively correlated with tumor stage, node metastasis and stromal invasion. Log-rank tests demonstrated that low expression of miR-483 was strongly correlated with poor overall survival in patients with gastric cancer. Moreover, ectopic expression of miR-483 remarkably suppressed gastric cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of gastric cancer cells, while low expression of miR-483 exhibited the opposite effect. Bioinformatics analysis revealed that OGT was a potential target of miR-483, and miR-483 inhibited the expression level of OGT mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-483 was negatively correlated with OGT in gastric cancer tissues. In addition, modulation of miR-483 expression could affect the global cellular protein O-GlcNAcylation in gastric cancer cells. Furthermore, silencing of OGT counteracted the effects of miR-483 repression, while its overexpression reversed tumor inhibitory effects of miR-483. In conclusion, our study revealed that miR-483 functions as a tumor suppressor by inhibiting proliferation, invasion and protein O-GlcNAcylation of gastric cancer via targeting OGT, and that miR-483 may serve as prognostic or therapeutic target for gastric cancer.