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lncRNA LOC100132354 promotes angiogenesis through VEGFA/VEGFR2 signaling pathway in lung adenocarcinoma

Authors Wang Y, Zhang F, Wang J, Hu L, Jiang F, Chen J, Chen J, Wang L

Received 15 June 2018

Accepted for publication 6 August 2018

Published 5 October 2018 Volume 2018:10 Pages 4257—4266

DOI https://doi.org/10.2147/CMAR.S177327

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Beicheng Sun


Yumin Wang,1,* Fan Zhang,1,* Junjun Wang,1 Lijuan Hu,1 Feng Jiang,1 Jian Chen,1 Jie Chen,2 Liangxing Wang3

1Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou China; 2Intensive Center Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou China; 3Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

*These authors contributed equally to this work

Purpose: This study aimed to study the biological function and the molecular mechanisms associated with the promotion of angiogenesis by lncRNA LOC100132354 in lung adenocarcinoma (LAD).
Patients and methods: The mRNA expression levels of 100 pairs of LAD and normal tissue samples of LOC100132354, vascular endothelial growth factor A (VEGFA), VEGF receptor-2 (VEGFR2), basic fibroblast growth factor (bFGF), and thrombospondin-1 (TSP-1) were analyzed by qPCR. LOC100132354 was knockdown and overexpressed in SPCA-1 and A549 cell lines to analyze the protein and mRNA expression levels of VEGFA, VEGFR2, bFGF, TSP-1, and changes in protein expression levels of Ras, P-A-Raf, P-B-Raf, P-C-Raf, P-Mekl/2, and P-Erk1/2. Tumor microvessel density (MVD) was analyzed in experimental nude mice.
Results: The qPCR results showed that the mRNA expression levels of LOC100132354, VEGFA, VEGFR2, and bFGF mRNA in LAD tissues were significantly increased, while TSP-1 mRNA was significantly decreased compared with the adjacent tissues. Survival analysis showed that VEGFA, VEGFR2, and bFGF were poor predictors, while TSP-1 was a good predictor in LAD. Knockdown or overexpression of LOC100132354 affected the expression levels of bFGF, VEGFA/VEGFR2 signaling pathway, and downstream target molecules, such as Ras, P-A-Raf, P-B-Raf, P-C-Raf, P-Mekl/2, and P-Erk1/2, while decreased TSP-1. After knockdown or overexpression of VEGFA expression, no significant changes in the expression level of LOC100132354 were found. Tumorigenesis of nude mice confirmed that LOC100132354 can significantly increase the tumor MVD.
Conclusion: These findings suggest VEGFA was a downstream target gene of LOC100132354, promoting angiogenesis through VEGFA/VEGFR2 signaling pathway and downstream target molecules in LAD. So, LOC100132354 is considered as an antiangiogenic target in LAD.

Keywords: lung cancer, lncRNA, angiogenesis, signaling pathway

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