title: Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A.
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.
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, General Hospital of Jinan Military Command, Jinan, China.
authors.forename: Lingmin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lv
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China. Center for Drug Discovery, Northeastern University, Boston, USA.
authors.forename: Changyan
authors.initials: C
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A