Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A

// Hongxia Chen 1, * , Lingmin Li 2, * , Shaojun Wang 3, * , Yupeng Lei 4, * , Qi Ge 4 , Nonghua Lv 4 , Xiaodong Zhou 4 , Changyan Chen 4, 5 1 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Nanchang University, Nanchang, China 2 Department of Gastroenterology, General Hospital of Jinan Military Command, Jinan, China 3 Department of Ophthalmology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China 4 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China 5 Center for Drug Discovery, Northeastern University, Boston, USA * Authors contribute equally to the project Correspondence to: Xiaodong Zhou, e-mail: [email protected] Nonghua Lv, e-mail: [email protected] Keywords: miR-126, gastric cancer, angiogenesis, VEGF, Akt/m-TOR phosphorylation Received: September 20, 2014      Accepted: October 27, 2014      Published: November 15, 2014 ABSTRACT miR-126 is an endothelial-specific microRNA essential for governing vascular integrity and angiogenesis. Its role in tumor angiogenesis of gastric cancer (GC) is unclear. This study aimed at determining the role of miR-126 in GC angiogenesis. Down-regulation of miR-126 was found to inversely correlate with an increased microvessel density (MVD) and vascular endothelial growth factor A (VEGF-A) expression in gastric cancer tissues. Bioinformatics analysis and luciferase reporter assay revealed that miR-126 directly targeted the 3'-untranslated region (3'-UTR) of VEGF-A mRNA. In addition, the restoration of miR-126 expression by lentivirus-miR-126 (Lenti-miR-126) transfection obviously reduced the expression of VEGF-A and the activition of its downstream genes, Akt, mTOR and Erk1/2 in gastric cancer cell lines SGC-7901, MKN-28 and MKN-45. In contrast, the down-regulation of miR-126 expression by lentivirus-anti-miR-126 (Lenti-anti-miR-126) transfection obviously up-regulated the expression of VEGF-A and its downstream signaling pathways. In vivo xenograft mice model experiments clarified the down-regulation of VEGF-A and MVD as well as inhibition of tumor growth by up-regulation of miR-126. Overall, the results from our study suggested that miR-126 could suppress tumor growth and tumor angiogenesis of GC through VEGF-A signaling, and it is a novel potential therapeutic target for GC.

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