MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers

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.

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells

“…Accumulating evidence further indicates that numerous miRNAs can impede cancer progression via direct suppression of VEGF-C. The miRNAs miR-101, miR-128, miR-206 and miR-1826 have been reported to inhibit tumour growth, lymphangiogenesis and metastasis by targeting VEGF-C in a variety of human cancer cells [24][25][26][47][48][49]. The present study showed that adiponectin markedly repressed miR-27b expression in human chondrosarcoma cells in vitro and in vivo.…”

CCL5 promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-507 in human chondrosarcoma cells

“…Deregulated biogenesis of miRNAs has been widely observed in human cancer [18]. Accumulating evidences further indicate that numerous miRNAs can impede cancer progression via direct suppression of VEGF-C. miR-27b, miR-101, miR-128, miR-206 and miR-1826 have been reported to inhibit tumor growth, lymphangiogenesis and metastasis by targeting VEGF-C in a variety of human cancer cells [20–22, 38–40]. Current study showed that CCL5 markedly repressed miR-507 expression in human chondrosarcoma cells in vitro and in vivo .…”

The regulatory role of microRNAs in angiogenesis‐related diseases

“…Overexpression miR-27b reduces the proliferation, migration and tube formation of HUVECs and decreases angiogenesis in colorectal cancer and gastric cancer via inhibiting the VEGFC/VEGFR2 signalling. 147,148 Moreover, a recent study indicated that miR-27b effectively represses migration and tube formation of ovarian cancer cells, and angiogenesis in vivo by inhibiting VE-cadherin. 145 In the bladder, prostate and colon tumours, miR-27b plays anti-tumour and anti-angiogenesis roles.…”