Oncotarget

Research Papers:

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

Hongxia Chen _, Lingmin Li, Shaojun Wang, Yupeng Lei, Qi Ge, Nonghua Lv, Xiaodong Zhou and Changyan Chen

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Oncotarget. 2014; 5:11873-11885. https://doi.org/10.18632/oncotarget.2662

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Abstract

Hongxia Chen1,*, Lingmin Li2,*, Shaojun Wang3,*, Yupeng Lei4,*, Qi Ge4, Nonghua Lv4, Xiaodong Zhou4, Changyan Chen4,5

1Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Nanchang University, Nanchang, China

2Department of Gastroenterology, General Hospital of Jinan Military Command, Jinan, China

3Department of Ophthalmology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China

4Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China

5Center 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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