Abstract
Vascular Endothelial Growth Factor C (VEGF-C) has critical roles in angiogenesis in human cancers; however, the underlying mechanisms regulating VEGF-C expression remain largely unknown. In the present study, VEGF-C protein expression and the density of blood vessels or lymphatic vessels were determined by immunohistochemistry in 103 cases of gastric cancer tissues. Suppression of VEGF-C by miR-27b, miR-101 and miR-128 was investigated by luciferase assays, Western blot and ELISA. The miRNAs expression levels were detected in human gastric cancers by real-time quantitative PCR. Cell proliferation, migration and invasion assays were performed to assess the effect of miRNAs on gastric cancer cells and human umbilical vascular endothelial cells (HUVECs). Our data showed that high VEGF-C expression was significantly associated with increased tumor size, advanced TNM classification and clinical stage, higher microvessel density (MVD) and lymphatic density (LVD), as well as poor survival in patients with gastric cancer. Furthermore, VEGF-C was found to be a direct target gene of miR-27b, miR-101, and miR-128. The expression levels of the three miRNAs were inversely correlated with MVD. Overexpression of miR-27b, miR-101, or miR-128 suppressed migration, proliferation activity, and tube formation in HUVECs by repressing VEGF-C secretion in gastric cancer cells. We conclude that miR-27b, miR-101 and miR-128 inhibit angiogenesis by down-regulating VEGF-C expression in gastric cancers.
Highlights
Expression of vascular endothelial growth factor-C (VEGF-C), a member of the platelet-derived growth factor family, correlates significantly with proliferation and migration of vascular endothelial cells, as well as lymphangiogenesis [6]
Vascular Endothelial Growth Factor C (VEGF-C) expression is up-regulated in human gastric cancer tissues
These results suggest that miR-27b, miR-101, or miR-128 attenuates tube formation of human umbilical vascular endothelial cells (HUVECs) induced by secreted VEGF-C from gastric cancer cells in vitro
Summary
Expression of vascular endothelial growth factor-C (VEGF-C), a member of the platelet-derived growth factor family, correlates significantly with proliferation and migration of vascular endothelial cells, as well as lymphangiogenesis [6]. VEGF-C has important roles in stimulating the development, and possibly the progression of tumors. Gastric cancer is the fourth most common cancer and is one of the leading causes of cancer-related death worldwide [1]. A multi-step progression to metastasis is the main cause of cancer-related death [3]. Angiogenesis facilitates the initial development of primary malignant neoplasms and progression of metastatic tumors [4]. Vascular proliferation and angiogenesis are closely involved in infiltration and metastasis of cancer cells [5]
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