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.
Highlights
Gastric cancer has long been one of the world’s major cancer especially in Asian countries
We mainly investigated the role of miR-126 on gastric cancer angiogenesis
The results have shown the reduced expression of miR-126 associated with higher microvessel density (MVD) and vascular endothelial growth factor A (VEGF-A) in gastric cancer
Summary
Gastric cancer has long been one of the world’s major cancer especially in Asian countries. The overall survival rate for patients with gastric carcinoma has increased, as a result of improved detection of early cancer and wider implementation of radical surgery, it still ranked the fourth most common cancer and might be the second leading cause of cancer death world widely [1,2,3]. Gastric cancer is aggressive in essence and a large number of even those patients who have early stage disease will eventually die from recurrence after definitive therapy. The overall outcome of patients is barely satisfactory due to metastasis and recurrence [1, 4]. Since angiogenesis is desirable for the development, progression, and metastasis www.impactjournals.com/oncotarget of various cancers [5], it has been wildly studied and antiangiogenesis continues to be the repeating theme of cancer therapy of the modern era. There is an urgent call for finding new therapeutic targets for antiangiogenesis of gastric cancer
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