MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers
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Hai-Ting Liu1, Ai-Yan Xing1, Xu Chen1, Ran-Ran Ma1, Ya-Wen Wang1, Duan-Bo Shi1, Hui Zhang1, Peng Li1, Hong-Fang Chen1,2, Yu-Hong Li1,3 and Peng Gao1
1 Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
2 Department of Pathology, Qingzhou Center Hospital, Weifang, P.R. China
3 Department of Pathology, Liaocheng Peoples Hospital, Liaocheng, P.R. China
Peng Gao, email:
Keywords: microRNA-27b, microRNA-101, microRNA-128, angiogenesis, gastric cancer
Received: July 18, 2015 Accepted: September 23, 2015 Published: October 09, 2015
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.
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